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Information on EC 1.1.1.42 - isocitrate dehydrogenase (NADP+)
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1.1.1.42 isocitrate dehydrogenase (NADP+)IUBMB Comments
Requires Mn2+ or Mg2+ for activity. Unlike EC 1.1.1.41, isocitrate dehydrogenase (NAD+), oxalosuccinate can be used as a substrate. In eukaryotes, isocitrate dehydrogenase exists in two forms: an NAD+-linked enzyme found only in mitochondria and displaying allosteric properties, and a non-allosteric, NADP+-linked enzyme that is found in both mitochondria and cytoplasm . The enzyme from some species can also use NAD+ but much more slowly [6,7].
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- 1.1.1.42
- glioma
- glioblastoma
- astrocytomas
- dehydrogenases
- malate
- leukemia
- myeloid
- glucose-6-phosphate
-
resect
-
oncometabolite
- oligodendrogliomas
- d-2-hydroxyglutarate
-
anaplastic
-
malic
-
idh1-mutant
-
tricarboxylic
-
hypermethylation
- multiforme
-
high-grade
-
progression-free
- temozolomide
- 2-oxoglutarate
-
radiotherapy
-
codeletion
-
neomorphic
- alpha-ketoglutarate
- 6-phosphogluconate
-
nadph-generating
- cholangiocarcinomas
-
o6-methylguanine-dna
-
gliomagenesis
- aconitase
-
oligodendroglial
- lgg
- chondrosarcoma
-
lower-grade
- oligoastrocytomas
- medicine
-
nadp-malic
-
supratentorial
- biotechnology
-
nadph-producing
- analysis
- diagnostics
- nadp-me
-
radiomics
-
pilocytic
-
karnofsky
-
proneural
The enzyme appears in viruses and cellular organisms
Reaction Schemes
+
=
+
+
+
Synonyms
isocitrate dehydrogenase 1, nadp-isocitrate dehydrogenase, nadp-dependent isocitrate dehydrogenase, isocitrate dehydrogenase-1, nadp-icdh, nadp-idh, nadp+-dependent isocitrate dehydrogenase, nadp-linked isocitrate dehydrogenase, nadp-specific isocitrate dehydrogenase, nadp+-specific isocitrate dehydrogenase, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
cICDH
CtIDP1
-
-
-
-
CtIDP2
-
-
-
-
cytosolic NADP+-dependent isocitrate dehydrogenase
cytosolic NADP-dependent isocitrate dehydrogenase
ICD
ICDH
ICDH-1
IDH
IDH-I
IDH-IIa
IDH-IIb
IDH1
IDH2
IDP
IDP1
IDP2
IDP3
IDPc
IDPm
isocitrate dehydrogenase
isocitrate dehydrogenase (NADP)
-
-
-
-
isocitrate dehydrogenase (NADP-dependent)
-
-
-
-
isocitrate dehydrogenase (nicotinamide adenine dinucleotide phosphate)
-
-
-
-
isocitrate dehydrogenase 1
isocitrate dehydrogenase 2
isocytrate deyhdrogenase
mitochondrial NADP+-dependent isocitrate dehydrogenase
NAD+-dependent isocitrate dehydrogenase
NADP isocitric dehydrogenase
-
-
-
-
NADP+-dependent IDH
NADP+-dependent isocitrate dehydrogenase
NADP+-ICDH
NADP+-IDH
NADP+-isocitrate dehydrogenase
NADP+-linked isocitrate dehydrogenase
-
-
-
-
NADP+-specific ICDH
-
-
-
-
NADP+-specific IDH
NADP+-specific isocitrate dehydrogenase
NADP-dependent IDH
NADP-dependent isocitrate dehydrogenase
NADP-dependent isocitric dehydrogenase
-
-
-
-
NADP-ICDH
NADP-IDH
NADP-isocitrate dehydrogenase
NADP-linked isocitrate dehydrogenase
-
-
-
-
NADP-specific isocitrate dehydrogenase
oxalosuccinate decarboxylase
-
-
-
-
oxalsuccinic decarboxylase
-
-
-
-
PS-NADP-IDH
-
-
-
-
TM1148
YlIDP
IDH
-
-
-
-
IDP
-
-
-
-
NADP+-dependent isocitrate dehydrogenase
-
-
NADP-dependent isocitrate dehydrogenase
-
-
-
-
NADP-specific isocitrate dehydrogenase
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
isocitrate + NADP+ = oxalosuccinate + NADPH + H+
(1a)
-
-
-
oxalosuccinate = 2-oxoglutarate + CO2
(1b)
-
-
-
isocitrate + NADP+ = 2-oxoglutarate + CO2 + NADPH + H+
active site structure and reaction mechanism, conformational changes at the active site resulting in closed and open forms, regulatory residues are isocitrate-binding Asp279and Ser94
-
isocitrate + NADP+ = 2-oxoglutarate + CO2 + NADPH + H+
active site structure contains a well-ordered Mn2+-isocitrate complex, reaction mechanism
isocitrate + NADP+ = 2-oxoglutarate + CO2 + NADPH + H+
Ser95, Asn97, and Thr78 are important for the catalysis having distinguishable functions, overview
-
isocitrate + NADP+ = 2-oxoglutarate + CO2 + NADPH + H+
Tyr140 and Lys212 are required for catalytic activity, Tyr140 is the general acid that protonates the substrate after decarboxylation, Lys212 lowers as a positively charged residue the pK of the nearby ionizable group in the enzyme-substrate complex and stabilizes the carbanion formed initially on substrate decarboxylation
isocitrate + NADP+ = 2-oxoglutarate + CO2 + NADPH + H+
overall reaction
-
-
-
isocitrate + NADP+ = 2-oxoglutarate + CO2 + NADPH + H+
protonation of the enolate to form product 2-oxoglutarate is the rate-limiting step
isocitrate + NADP+ = 2-oxoglutarate + CO2 + NADPH + H+
overall reaction, catalytic mechanism, overview. The catalysis proceeds in three steps: (1) NADP+ reduction by the isocitrate substrate with the help of the Lys212B base, (2) beta-decarboxylation of the resulting oxalosuccinate, generating an enolate, and (3) protonation of this intermediate by Tyr139A, giving rise to the 2-oxooglutarate product. The beta-decarboxylation of oxalosuccinate is the most likely rate-limiting step. Role of Mg2+ and Asp275A, whose acid/base properties throughout the catalytic cycle lower the barrier to physiologically competent values. The catalysis takes place in a closed-conformation quaternary complex and involves significant conformational changes as the divalent metal (Mg2+ or Mn2+), the NADP+ cofactor, and the trianionic form of the isocitrate substrate (ICT) sequentially bind
-
isocitrate + NADP+ = 2-oxoglutarate + CO2 + NADPH + H+
protonation of the enolate to form product 2-oxoglutarate is the rate-limiting step
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidative decarboxylation
-
-
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-
redox reaction
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-
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reductive carboxylation
-
-
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PATHWAY SOURCE
PATHWAYS
KEGG
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citric acid cycle, citric acid cycle, Glutathione metabolism, Microbial metabolism in diverse environments, Microbial metabolism in diverse environments, Microbial metabolism in diverse environments, Microbial metabolism in diverse environments, Microbial metabolism in diverse environments, Microbial metabolism in diverse environments, Microbial metabolism in diverse environments, Microbial metabolism in diverse environments, Microbial metabolism in diverse environments
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SYSTEMATIC NAME
IUBMB Comments
isocitrate:NADP+ oxidoreductase (decarboxylating)
Requires Mn2+ or Mg2+ for activity. Unlike EC 1.1.1.41, isocitrate dehydrogenase (NAD+), oxalosuccinate can be used as a substrate. In eukaryotes, isocitrate dehydrogenase exists in two forms: an NAD+-linked enzyme found only in mitochondria and displaying allosteric properties, and a non-allosteric, NADP+-linked enzyme that is found in both mitochondria and cytoplasm [6]. The enzyme from some species can also use NAD+ but much more slowly [6,7].
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CAS REGISTRY NUMBER
COMMENTARY
9028-48-2
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2-oxoglutarate + NADPH + H+
2-hydroxyglutarate + NADP+
the reaction is catalyzed by mutant enzymes R153H and R153C
-
-
?
(2R,3S)-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
slow reaction
-
-
?
(2R,3S)-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
slow reaction
-
-
?
(2R,3S)-isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH
-
-
-
?
(2R,3S)-isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH
Thermus thermophilus HB8 / ATCC 27634 / DSM 579
-
-
-
?
2-oxoglutarate + NADPH + H+
D-2-hydroxyglutarate + NADP+
the reaction is catalyzed by diverse R132 mutant enzymes
-
-
r
2-oxoglutarate + NADPH + H+
D-2-hydroxyglutarate + NADP+
the reaction is catalyzed by mutant enzyme R132H
-
-
r
D-isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH
-
enzyme is an integral part of the mitochondrial TCA cycle, and it is involved in providing NADPH for reductive reactions in the cell
-
-
?
D-isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH
-
the reaction is reversible for isozyme IDP2
-
-
r
DL-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH
Q8X277
NAD+ is only substrate for mutant R291S/K343D/Y344I/V350A/Y390P
-
-
?
DL-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH + H+
-
low activityy with NAD+
-
-
?
DL-isocitrate + NAD+
2-oxoglutarate + CO2 + NADH + H+
-
low activityy with NAD+
-
-
?
DL-isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH
Q8X277
NAD+ is not substrate for mutant R291S/K343D/Y344I/V350A/Y390P
-
-
?
DL-isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH
-
-
-
-
?
DL-isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
?
DL-isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
r
DL-isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
NADP+ is the highly preferred cofactor
-
-
?
DL-isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
-
?
DL-isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
NADP+ is the highly preferred cofactor
-
-
?
DL-isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
ir
DL-isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
carboxylation of 2-oxoglutarate to produce isocitrate
-
-
ir
isocitrate + APADP+
2-oxoglutarate + CO2 + APADPH
60% activity compared to NAD+
-
-
r
isocitrate + APADP+
2-oxoglutarate + CO2 + APADPH
60% activity compared to NAD+
-
-
r
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH + H+
engineered enzyme mutant D253A/S257K/K260Q/R314D/H315I/T327A, cf. EC 1.1.1.41
-
-
r
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH + H+
engineered enzyme mutant D253A/S257K/K260Q/R314D/H315I/T327A, cf. EC 1.1.1.41
-
-
r
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH + H+
the reaction is catalyzed by mutant enzymes H590L/R601D/R650S and H590L/R601D
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH + H+
the reaction is catalyzed by mutant enzymes H590L/R601D/R650S and H590L/R601D
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH + H+
Km-value for NAD+ is 34fold higher compared to KM-value for NADP+
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH + H+
Km-value for NAD+ is 34fold higher compared to KM-value for NADP+
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH + H+
low activity with mutant enzyme R322D, no activity with the wild-type enzyme
-
-
r
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH + H+
low activity with mutant enzyme R322D, no activity with the wild-type enzyme
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
overall reaction
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
strict substrate and coenzyme specificity
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
carbon dioxide-fixing enzyme in the reductive tricarboxylic acid cycle, preference for carboxylation reaction direction
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
metabolic regulation, involved in the tricarboxylic acid cycle
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
the enzyme shows high substrate specificity
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
key enzyme of the tricarboxylic acid cycle
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
enzyme has a self-regulatory mechanism of activity mimicking the phosphorylation mechanism of bacterial enzymes
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
100% actiivty
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
100% actiivty
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
cytosolic enzyme is critical in fat and cholesterol biosynthesis, enzyme content correlates with adipogenesis in wild-type adipocytes and in transgenic cells
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
the cytosolic isozyme supplies 2-oxoglutarate for the photorespiratory ammonia fixation, pyridine nucleotide contents in mitochondria and cytosol, regulation, overview
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
the enzyme could have a protective antioxidant role against certain environmental stresses in plants
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
isocitrate dehydrogenase is an important NADPH-generating enzyme in the endoplasmic reticulum
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
metabolic regulation, involved in the tricarboxylic acid cycle
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
metabolic regulation, involved in the tricarboxylic acid cycle
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
Km-value for NAD+ is 34fold higher compared to KM-value for NADP+
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
Km-value for NAD+ is 34fold higher compared to KM-value for NADP+
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
isozymes are compartment interchangeable for glutamate synthesis, although mitochondrial localization has a positive impact on this function during fermentative growth
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
reaction is reversible for isozymes IDP1 and IDP2
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
metabolic regulation of the isozymes
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
Ser95, Asn97, and Thr78 are involved in substrate binding
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
low activity with NAD+. Km-value for NAD+ is about 140fold higher than the KM-value for NADP+
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
low activity with NAD+. Km-value for NAD+ is about 140fold higher than the KM-value for NADP+
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
r
isocitrate + NADP+
2-oxoglutarate + NADPH + H+ + CO2
-
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + NADPH + H+ + CO2
-
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + NADPH + H+ + CO2
-
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + NADPH + H+ + CO2
-
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + NADPH + H+ + CO2
-
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + NADPH + H+ + CO2
-
IDH1 is an enzyme that catalyzes the oxidative decarboxylation of isocitrate into alpha-ketoglutarate utilizing either NAD+ or NADP+ as cosubstrates
-
-
?
isocitrate + NADP+
2-oxoglutarate + NADPH + H+ + CO2
-
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + NADPH + H+ + CO2
-
-
-
-
?
isocitrate + NHDP+
2-oxoglutarate + CO2 + NHDPH
2.0% activity compared to NAD+
-
-
r
isocitrate + NHDP+
2-oxoglutarate + CO2 + NHDPH
2.0% activity compared to NAD+
-
-
r
additional information
?
-
-
the enzyme is a substrate for Escherichia coli isocitrate dehydrogenase kinase/phosphatase
-
-
-
additional information
?
-
the enzyme is a substrate for Escherichia coli isocitrate dehydrogenase kinase/phosphatase
-
-
-
additional information
?
-
NADP+-dependent isocitrate dehydrogenase may play an important role in regulating the apoptosis induced by heat shock
-
-
?
additional information
?
-
-
NADP+-dependent isocitrate dehydrogenase may play an important role in regulating the apoptosis induced by TNF-alpha and anticancer drugs
-
-
?
additional information
?
-
the R132H mutant IDH1 directly converts 2-oxoglutarate to 2-hydroxyglutarate, that rapidly accumulates in the medium of cells expressing R132H mutant IDH1
-
-
?
additional information
?
-
-
the R132H mutant IDH1 directly converts 2-oxoglutarate to 2-hydroxyglutarate, that rapidly accumulates in the medium of cells expressing R132H mutant IDH1
-
-
?
additional information
?
-
the enzyme is highly specific to NADP+ and cannot utilize NAD+
-
-
-
additional information
?
-
the enzyme is highly specific to NADP+ and cannot utilize NAD+
-
-
-
additional information
?
-
-
enzyme plays an important regulatory role in cellular defense against oxidative stress and in senescence
-
-
?
additional information
?
-
-
NADP+-dependent isocitrate dehydrogenase plays an important protective role in apoptosis of HL-60 cells induced by singlet oxygen
-
-
?
additional information
?
-
-
IDPm expression in HepG2 cells regulates ethanol-induced toxicity
-
-
?
additional information
?
-
Mycobacterium tuberculosis ICDH-1 also catalyzes the formation of 2-hydroxyglutarate
-
-
?
additional information
?
-
-
Mycobacterium tuberculosis ICDH-1 also catalyzes the formation of 2-hydroxyglutarate
-
-
?
additional information
?
-
Mycobacterium tuberculosis ICDH-1 also catalyzes the formation of 2-hydroxyglutarate
-
-
?
additional information
?
-
-
no activity Is detected when 0.12 mM NAD+, instead of NADP+, is added to the reaction mixture
-
-
-
additional information
?
-
-
86% of total activity in the cell, main factor for synthesis of 2-oxoglutarate. Enzyme and cytoplasmic aspartate aminotransferase are regulated oppositely and the catalytic activity of one enzyme can be stimulated concurrently with a decrease in the activity of the other
-
-
?
additional information
?
-
suppression of enzyme activity by small interfering RNA results in impairment of glucose-stimulated insulin secretion, attenuates glucose-induced increments in pyruvate cycling activity and in NADPH levels, and causes increases in lactate production
-
-
?
additional information
?
-
-
His319 and His315 are not responsible for enzyme Fe2+-isocitrate cleavage
-
-
?
additional information
?
-
-
during oxidative stress, enzyme activity appears to be modulated through enzymatic glutathionylation and deglutathionylation
-
-
?
additional information
?
-
the isocitrate molecule is located at the active site, and interacts with residues at the cleft between the large and small domain. The catalytic triad residues Lys191, Asp248 and Tyr144 are conserved and interact with isocitrate
-
-
?
additional information
?
-
-
the isocitrate molecule is located at the active site, and interacts with residues at the cleft between the large and small domain. The catalytic triad residues Lys191, Asp248 and Tyr144 are conserved and interact with isocitrate
-
-
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
D-isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH
-
enzyme is an integral part of the mitochondrial TCA cycle, and it is involved in providing NADPH for reductive reactions in the cell
-
-
?
D-isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH
-
the reaction is reversible for isozyme IDP2
-
-
r
DL-isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
?
DL-isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
r
DL-isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
-
?
DL-isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
ir
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
overall reaction
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
strict substrate and coenzyme specificity
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
carbon dioxide-fixing enzyme in the reductive tricarboxylic acid cycle, preference for carboxylation reaction direction
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
metabolic regulation, involved in the tricarboxylic acid cycle
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
key enzyme of the tricarboxylic acid cycle
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
enzyme has a self-regulatory mechanism of activity mimicking the phosphorylation mechanism of bacterial enzymes
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
cytosolic enzyme is critical in fat and cholesterol biosynthesis, enzyme content correlates with adipogenesis in wild-type adipocytes and in transgenic cells
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
the cytosolic isozyme supplies 2-oxoglutarate for the photorespiratory ammonia fixation, pyridine nucleotide contents in mitochondria and cytosol, regulation, overview
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
the enzyme could have a protective antioxidant role against certain environmental stresses in plants
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
isocitrate dehydrogenase is an important NADPH-generating enzyme in the endoplasmic reticulum
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
metabolic regulation, involved in the tricarboxylic acid cycle
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
metabolic regulation, involved in the tricarboxylic acid cycle
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
isozymes are compartment interchangeable for glutamate synthesis, although mitochondrial localization has a positive impact on this function during fermentative growth
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
metabolic regulation of the isozymes
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
r
isocitrate + NADP+
2-oxoglutarate + NADPH + H+ + CO2
-
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + NADPH + H+ + CO2
-
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + NADPH + H+ + CO2
-
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + NADPH + H+ + CO2
-
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + NADPH + H+ + CO2
-
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + NADPH + H+ + CO2
-
IDH1 is an enzyme that catalyzes the oxidative decarboxylation of isocitrate into alpha-ketoglutarate utilizing either NAD+ or NADP+ as cosubstrates
-
-
?
isocitrate + NADP+
2-oxoglutarate + NADPH + H+ + CO2
-
-
-
-
?
isocitrate + NADP+
2-oxoglutarate + NADPH + H+ + CO2
-
-
-
-
?
additional information
?
-
NADP+-dependent isocitrate dehydrogenase may play an important role in regulating the apoptosis induced by heat shock
-
-
?
additional information
?
-
-
NADP+-dependent isocitrate dehydrogenase may play an important role in regulating the apoptosis induced by TNF-alpha and anticancer drugs
-
-
?
additional information
?
-
the R132H mutant IDH1 directly converts 2-oxoglutarate to 2-hydroxyglutarate, that rapidly accumulates in the medium of cells expressing R132H mutant IDH1
-
-
?
additional information
?
-
-
the R132H mutant IDH1 directly converts 2-oxoglutarate to 2-hydroxyglutarate, that rapidly accumulates in the medium of cells expressing R132H mutant IDH1
-
-
?
additional information
?
-
-
enzyme plays an important regulatory role in cellular defense against oxidative stress and in senescence
-
-
?
additional information
?
-
-
NADP+-dependent isocitrate dehydrogenase plays an important protective role in apoptosis of HL-60 cells induced by singlet oxygen
-
-
?
additional information
?
-
-
IDPm expression in HepG2 cells regulates ethanol-induced toxicity
-
-
?
additional information
?
-
-
86% of total activity in the cell, main factor for synthesis of 2-oxoglutarate. Enzyme and cytoplasmic aspartate aminotransferase are regulated oppositely and the catalytic activity of one enzyme can be stimulated concurrently with a decrease in the activity of the other
-
-
?
additional information
?
-
suppression of enzyme activity by small interfering RNA results in impairment of glucose-stimulated insulin secretion, attenuates glucose-induced increments in pyruvate cycling activity and in NADPH levels, and causes increases in lactate production
-
-
?
additional information
?
-
-
during oxidative stress, enzyme activity appears to be modulated through enzymatic glutathionylation and deglutathionylation
-
-
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NADP+
-
Arg314 and the aromatic ring of Tyr316 are important for affinity to the cofactor and catalysis, interaction with 2'-phosphate group of NADP+
NADP+
-
binding of 1 mol NADP+ per enzyme subunit, His309 is highly important for cofactor binding, HIs315 is involved, while His319 is not
NADP+
-
binding site structure, interaction with the 2'-phosphate group of the ribose moiety
NADP+
the recombinant IDH displays a 62000fold (kcat/Km) preference for NADP+ over NAD+ with Mn2+, and a 85000fold greater specificity for NADP+ than NAD+ with Mg2+
NADP+
NADP+-binding site in the interdomain interface, the enzyme shows high specificity for NADP+ mediated by interactions with the negatively charged 2'-phosphate group, which is surrounded by the side chains of two arginines, one histidine and, via a water, one lysine residue, forming ion pairs and hydrogen bonds
NADP+
purified recombinant MaIDH is completely specific with NADP+, and no NAD+-dependent activity is detectable
NADP+
-
NADP+ is anchored in the active site by a tetrad composed of Lys72A, Thr75A, Asn96A, and Glu306A
NADP+
the enzyme is completely NADP+-dependent and no NAD+-linked activity is detectable
NADP+
the catalytic efficiency for NAD+ is 5times higher for NAD+ than for NADP+
NADP+
-
the enzyme isoform IDH-90 exclusively catalyzes the reduction of NADP+
additional information
-
SdIDH displays a 19000-32000fold (kcat/Km) preference for NADP+ over NAD+ with Mn2+ and Mg2+, respectively
-
additional information
the enzyme is completely inactive with NAD+
-
additional information
the enzyme is completely inactive with NAD+
-
additional information
enzyme YlIDP is absolutely dependent on NADP+ and shows no NAD-dependent activity
-
additional information
the enzyme shows a 567 and 193fold preference for NADP+ over NAD+ in the presence of Mg2+ and Mn2+, respectively. The coenzyme specificity of BlIDH can be completely reversed from NADP+ to NAD+ by a factor of 2387 by replacing six residues by rational mutagenesis
-
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Cd2+
Co2+
KCl
-
the activity of the enzyme is markedly dependent on the concentration of NaCl or KC1 in the Tris/EDTA/Mg2+ buffer, being maximal in 0.5 M NaCl or KCl. The stimulatory effect of KCl is greater than that of NaCl
Li+
Mg2+
Mn2+
Na+
NaCl
-
the activity of the enzyme is markedly dependent on the concentration of NaCl or KC1 in the Tris/EDTA/Mg2+ buffer, being maximal in 0.5 M NaCl or KCl. The stimulatory effect of KCl is greater than that of NaCl
Ni2+
Zn2+
additional information
Ca2+
-
divalent metal ion is required, binding structure and conformation at the isocitrate-metal-binding site
Cd2+
the enzyme activity is increased at a Cd2+ concentration below 0.1 mM
Mg2+
-
divalent cation is required, optimal activity at 40 mM in the forward reaction, and at 250 mM in the reverse reaction
Mg2+
-
divalent metal ion is required, binding structure and conformation at the isocitrate-metal-binding site
Mg2+
Mg2+ can partially replace the activation of Mn2+ (40.3%). 2 mM used in assay conditions
Mg2+
Mg2+ can act as a significant substitute by providing up to 58-75% of the enzyme's maximal activity
Mg2+
the maximum activity with Mg2+ is slightly lower than that with Cd2+
Mg2+
-
divalent cation is required, optimal activity at 2 mM in the forward reaction, and at 200 mM in the reverse reaction
Mg2+
-
activates, about 50% activity compared to Mn2+, SdIDH displays a 19000-32000fold (kcat/Km) preference for NADP+ over NAD+ with Mn2+ and Mg2+, respectively
Mg2+
the recombinant IDH displays a 85000fold greater specificity for NADP+ than NAD+ with Mg2+
Mn2+
-
divalent cation is required, optimal activity at 10 mM in the forward reaction, and at 50 mM in the reverse reaction
Mn2+
Mn2+ is the most favored cation, 2 mM used in assay conditions
Mn2+
KM-value for enzyme from normoxic heart, 0.42 mM, for enzyme from ischemic heart 0.15 mM
Mn2+
Km-value: 0.42 mM for enzyme from normoxic heart, 0.15 mM for enzyme from ischemic heart
Mn2+
-
divalent cation is required, optimal activity at 1 mM in the forward reaction, and at 20 mM in the reverse reaction
Mn2+
-
activates, preferred cation, SdIDH displays a 19000-32000fold (kcat/Km) preference for NADP+ over NAD+ with Mn2+ and Mg2+, respectively
Mn2+
the recombinant IDH displays a 62000fold (kcat/Km) preference for NADP+ over NAD+ with Mn2+
Mn2+
-
as Mn2+-isocitrate complex, Ser95, Asn97, and Thr78 are involved in binding
Mn2+
-
Mn2+ is the most favored divalent cation. Mn2+ can be partly replaced by Mg2+ (17.6% activity). 2 mM is used in assay conditions
Zn2+
a zinc ion is tightly bound to Asp301, Asp305, Asp277 in the active site of subunit A and subunit B
Zn2+
NADP+-linked activity at pH 8.5 is fully activated by the presence of Zn2+
additional information
the enzyme is dependent on divalent cations, overview. No activity with Zn2+, Cu2+, Ca2+, and Li+,very low activity with K+, Na+, Ni2+, and Rb+
additional information
Ni2+, Co2+, Na+, K+ and Li+ have almost no effect on the activity of the enzyme when assayed in the presence of Mn2+
additional information
-
the enzyme is completely divalent cation dependent. As compared with Mn2+, MaIDH shows about 2.5times and 4times higher affinities (1/Km) to NADP+ and DL-isocitrate with Mg2+, Cu2+ does not activate the enzyme at all
additional information
the enzyme is completely divalent cation dependent. As compared with Mn2+, MaIDH shows about 2.5times and 4times higher affinities (1/Km) to NADP+ and DL-isocitrate with Mg2+, Cu2+ does not activate the enzyme at all
additional information
-
no acitivty of isoforms with Mn2+ or Ca2+
additional information
the enzyme is absolutely divalent cation dependent, no or poor activation by Ca2+, Zn2+, K+, Na+, and Rb+
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(+)-ML309
reversible binding analysis and mechanism, detailed overview. The reversible inhibitor binds to IDH1 R132H competitively with respect to 2-oxoglutarate and uncompetitively with respect to NADPH. ML309 competes with 2-oxoglutarate but is uncompetitive with NADPH and rapidly and reversibly affects cellular 2-hydroxyglutarate levels. The rapidly equilibrating inhibitor is active in both biochemical and cellular assays. The (+) isomer is active, whereas the (-) isomer is over 400fold less active for IDH1 R132H inhibition. IDH1 R132C is similarly inhibited by (-)-ML309. ML309 is also able to inhibit 2-hydroxyglutarate production in a glioblastoma cell line and had minimal cytotoxicity. In the presence of racemic ML309, 2-hydroxyglutarate levels drop rapidly
(-)-ML309
reversible binding analysis and mechanism, detailed overview. The reversible inhibitor binds to IDH1 R132H competitively with respect to 2-oxoglutarate and uncompetitively with respect to NADPH. ML309 competes with 2-oxoglutarate but is uncompetitive with NADPH and rapidly and reversibly affects cellular 2-hydroxyglutarate levels. The rapidly equilibrating inhibitor is active in both biochemical and cellular assays. The (+) isomer is active, whereas the (-) isomer is over 400fold less active for IDH1 R132H inhibition. IDH1 R132C is similarly inhibited by (-)-ML309. Wild-type IDH1 is largely unaffected by (+)-ML309. ML309 is also able to inhibit 2-hydroxyglutarate production in a glioblastoma cell line and had minimal cytotoxicity. In the presence of racemic ML309, 2-hydroxyglutarate levels drop rapidly
(5aS,6S,9aR)-2-benzoyl-6-methyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile
-
(5aS,6S,9aR)-6-methyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile
-
(6aS,7S,10aR)-2-anilino-7-methyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile
-
(6aS,7S,10aR)-7,10a-dimethyl-8-oxo-2-(phenylamino)-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile
-
(6aS,7S,10aR)-7-methyl-8-oxo-10a-phenyl-2-[(pyridin-3-yl)amino]-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile
-
(6aS,7S,10aR)-7-methyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile
-
(6aS,7S,10aS)-2-anilino-7-methyl-10a-phenyl-5,6a,7,10a-tetrahydrobenzo[h]quinazolin-8(6H)-one
-
(7R)-1-[(4-fluorophenyl)methyl]-N-[3-[(1R)-1-hydroxyethyl]phenyl]-7-methyl-5-(1H-pyrrole-2-carbonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-3-carboxamide
-
3-morpholinosydnonimine
44% inhibition at 5 mM of leaf and root enzymes
3-[(5aS,6S,9aR)-8-cyano-6-methyl-7-oxo-2,4,5,5a,6,7-hexahydro-9aH-benzo[g]indazol-9a-yl]benzoic acid
-
3-[(6aS,7S,10aR)-2-anilino-9-cyano-7-methyl-8-oxo-6,6a,7,8-tetrahydrobenzo[h]quinazolin-10a(5H)-yl]benzoic acid
-
4-hydroxynonenal
-
50% inhibition at 37°C, after 1 h at 0.5 mM, lipid peroxidation product, enzyme becomes susceptible to oxidative damage leading to structural alterations, carbonylation
Fe2+
the inhibitory effect of the Fe2+ and H2O2 mixture associated with the generation of hydroxyl radicals is lower in enzyme from ischemic heart compared to enzyme from normoxic heart
glutathione disulfide
-
incubation with 5 mM glutathione disulfide for 30 min completely eliminates activity
glyoxalate
-
20% inhibition at 1 mM, presence of 1 mM oxaloacetate results in 50% inhibition
GSH
inhibits the leaf enzyme by 40% at 5 mM, but not the root enzyme
GSSG
increasing GSSG concentrations progressively inhibit the enzyme activity, almost complete inhibition at 1 mM
lipid hydroperoxide
-
50% inhibition at 37°C, after 1 h at 0.05 mM, lipid peroxidation product, enzyme becomes susceptible to oxidative damage leading to structural alterations, carbonylation
liposome
-
ICDH activity is enhanced with liposomes at 5 mol% cardiolipin, but inhibited at 30 mol% cardiolipin. 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine liposomes do not affect the activity of ICDH
-
malondialdehyde
-
50% inhibition at 37°C, after 1 h at 5 mM, lipid peroxidation product, enzyme becomes susceptible to oxidative damage leading to structural alterations, carbonylation
Mn2+
the specific activity of purified enzyme is increased by Mn2+ in the micromolar range
NaCl
-
isoform ICD-2, increase in activity in up to 200 mM NaCl. Isoform ICD-1, no influence of NaCl. Above 200 mM, NaCl is inhibitory
NaHS
2 and 10 mM NaHS used as H2S donors result in a decrease in enzyme activity of up to 36% and 45%, respectively
nitrosoglutathione
increasing nitrosoglutathione concentrations progressively inhibit the enzyme activity, complete inhibition at 2 mM
S-nitrosoglutathione
70.5% inhibition at 5 mM of the leaf enzyme, 37.3% of the root enzyme
2-oxoglutarate
-
50% inhibition of the forward reaction at 1.5 mM, 99% inhibition at 15 mM
2-oxoglutarate
-
50% inhibition of the forward reaction at 1.5 mM, 95% inhibition at 15 mM
2-oxoglutarate
-
isozymes ICDH2 and ICDH1, isozyme ICDH2 is more sensitive to negative feedback inhibition by 2-oxoglutarate
Ca2+
in the presence of Mn2+, Ca2+ strongly inhibits the activity of the enzyme (28.52% residual activity)
Cd2+
-
inhibits the purified enzyme and the enzyme in cells, NADP+ does not protect. No inhibition of IDPc mutant S269S. DNA fragmentation is enhanced in IDPc siRNA-transfected HEK293 cells compared to control cells upon exposure to cadmium
Cd2+
-
coadministration with oxalomalate results in inhibition of enzyme and glutaredoxin and enhanced susceptibility to apoptosis
Cd2+
above 0.1 mM, the enzyme loses activity, and at 2 mM Cd2+ most of the activity has disappeared. Chelation of Cd2+ by dithiothreitol cannot recover the lost enzyme activity. Inactivation of the enzyme by Cd2+ is less effective when the enzyme is activated with Cd2+ than Mg2+, More than 50% of the activity of the enzyme activated with 0.05 mM Cd2+ remains in the presence of 1 mM GSH
Cd2+
-
binds to C379 of enzyme, resulting in loss of activity and structural alterations. Loss of glutaredoxin activity in cells treated with Cd2+ is more pronounced when cells are transfected with enzyme antisense cDNA
Cu2+
-
enzyme is completely inhibited at 5 mM in presence of 5 mM Mg2+, organism is a copper-tolerant basidiomycete
glutathione
-
oxidized glutathione leads to enzyme inactivation with simultaneous formation of a mixed disulfide between glutathione and the cysteine residues of enzyme. Enzymical reactivation by glutaredoxin2 in presence of reduced glutathione
glyoxylate
-
18% inhibition at 5 mM, mixed type inhibition together with oxaloacetate, completely at 5 mM each
H2O2
affects the root enzyme slightly but not the enzyme from leaves
H2O2
the inhibitory effect of the Fe2+ and H2O2 mixture associated with the generation of hydroxyl radicals is lower in enzyme from ischemic heart compared to enzyme from normoxic heart
HOCl
i.e. hypochlorous acid, the HOCl-mediated damage to NADP+-dependent isocitrate dehydrogenase mayesult in perturbation of the cellular antioxidant defense mechanism and subsequently lead to a pro-oxidant condition
isocitrate
-
50% inhibition of the reverse reaction at 0.1 mM, 97% inhibition at 1.2 mM
isocitrate
-
70% inhibition of the reverse reaction at 0.1 mM, 99% inhibition at 1.2 mM
manganese(III) 5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrin
-
a superoxide dismutase mimic, ICD is inactivated by superoxide, but the inactivated enzyme is replaced by de novo protein synthesis
manganese(III) 5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrin
-
a superoxide dismutase mimic
NADPH
product inhibition competitive versus NADP+ and noncompetitive versus isocitrate
oxaloacetate
-
competitive, inhibits the reverse reaction, over 50% inhibition at 1 mM, synergistically with glyoxylate
oxaloacetate
-
41% inhibition at 5 mM, mixed type inhibition together with glyoxylate, completely at 5 mM each
oxaloacetate
-
25% inhibition at 1 mM, presence of 1 mM glyoxalate results in 50% inhibition
Oxalomalate
-
competitive, coadministration with CD2+ results in inhibition of enzyme and glutaredoxin and enhanced susceptibility to apoptosis
peroxynitrite
causes a 26% inhibition in enzyme activity with 5 mM SIN-1
peroxynitrite
-
ethanol toxicity is mediated by peroxynitrite and the peroxynitrite-mediated damage to NADP+-dependent isocitrate dehydrogenase and superoxide dismutase may be resulting in the perturbation of the cellular antioxidant defense systems and subsequently lead to a pro-oxidant condition
phosphoenolpyruvate
-
allosteric inhibition. Phosphoenolpyruvate enhances the uncompetitive inhibition of isocitrate lyase by increasing isocitrate, which protects isocitrate dehydrogenase from the inhibition, and contributes to the control through the tricarboxylic acid cycle and glyoxylate shunt
Zn2+
in the presence of Mn2+, Zn2+ strongly inhibits the activity of the enzyme (42.59% residual activity)
additional information
increasing concentrations of H2O2 hardly affect the enzyme activity
-
additional information
-
increasing concentrations of H2O2 hardly affect the enzyme activity
-
additional information
-
no inhibition of carboxylation by citrate, pyruvate, succinate, fumarate, malate, glyoxylate, ATP, and ADP
-
additional information
-
AMP is a no inhibitor, no inhibition by glutamate, pyruvate and succinate
-
additional information
-
transfection of HeLa cells with an IDPc small interfering RNA decreases activity of IDPc by 80%, enhancing the susceptibility of staurosporine-induced apoptosis reflected by DNA fragmentation, cellular redox status and the modulation of apoptotic marker proteins
-
additional information
-
5 mM glutathione does not noticeably inhibit IDPc activity
-
additional information
-
tumor-derived mutant IDH1 dominantly inhibits the wild-type IDH1 by forming a catalytically inactive heterodimer, resulting in a decrease of cellular 2-oxoglutarate
-
additional information
the enzyme is unaffected by the addition of 5 mM L-glutamate, L-glutamine, 2-oxoglutarate, oxaloacetate, cis-aconitate, citrate, pyruvate, malate, fumarate, succinate, CoA, AcCoA, NADH, and NADPH or 2 mM ADP and AMP
-
additional information
-
ischemia-reperfusion significantly reduces IDPc expression and activity
-
additional information
ischemia-reperfusion reduces IDH2 expression and activity in both Idh2+/+ and Idh2-/- kidneys
-
additional information
product inhibition patterns for ICDH-1, overview
-
additional information
-
product inhibition patterns for ICDH-1, overview
-
additional information
-
poor inhibition of the forward reaction by 2-oxoglutarate, no inhibition by CO2
-
additional information
-
enzyme is not affected by gamma-aminobutyric acid and succinate
-
additional information
-
activity is not affected by the nonspecific binding of the mitochondrial isozyme, not the cytosolic one, to 5'-untranslated regions of yeast mitochondrial mRNAs
-
additional information
-
no inhibition by phosphoenolpyruvate, fructose 1,6-bisphosphate, and pyruvate
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
acetic acid
mutant Y140T, 106fold activation compared to the wild-type enzyme
liposome
-
ICDH activity is enhanced with liposomes at 5 mol% cardiolipin, but inhibited at 30 mol% cardiolipin. 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine liposomes did not affect the activity of ICDH
-
NaCl
-
isoform ICD-2, increase in activity in up to 200 mM NaCl. Isoform ICD-1, no influence of NaCl. Above 200 mM, NaCl is inhibitory
paraquat
administration at 0.01 mM to roots results in remarkable induction of enzyme gene expression and dramatic increase of gene activity
SIRT3
under calorie restriction, mitochondrial deacetylase Sirt3 deacetylates and activates isoform IDH2
-
additional information
-
enzyme is not affected by gamma-aminobutyric acid and succinate
-
additional information
-
the mitochondrial isozyme is light-inducible, while the cytosolic one is not
-
additional information
-
applied oxidative stress leads to upregulation of enzyme expression in erythrocytic stages
-
additional information
-
glucose induces epression of isozyme IDP1, glycerol induces epression of isozymes IDP1 and IDP2, fatty acids induce epression of isozymes IDP1, IDP2, and IDP3
-
additional information
-
isozyme IDP3 is inducible by fatty acids, isozyme IDP2 by non-fermentable carbon sources, expression of isozyme IDP1 is constitutive
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.04
2-oxoglutarate
wild type enzyme, in Bis-Tris buffer, at pH 6.2 and 37°C
0.12
2-oxoglutarate
wild type enzyme, in Bis-Tris buffer, at pH 6.5 and 37°C
0.14
2-oxoglutarate
wild type enzyme, in Bis-Tris buffer, at pH 6.8 and 37°C
0.246
2-oxoglutarate
wild type enzyme, in Tris buffer, at pH 7.5 and 37°C
0.26
2-oxoglutarate
wild type enzyme, in Bis-Tris buffer, at pH 7.0 and 37°C
0.28
2-oxoglutarate
wild type enzyme, in potassium phosphate buffer, at pH 7.2 and 37°C
0.46
2-oxoglutarate
wild type enzyme, in potassium phosphate buffer, at pH 7.5 and 37°C
0.6
2-oxoglutarate
wild type enzyme, in potassium phosphate buffer, at pH 6.2 and 37°C
0.65
2-oxoglutarate
wild type enzyme, in potassium phosphate buffer, at pH 6.8 and 37°C
0.71
2-oxoglutarate
wild type enzyme, in potassium phosphate buffer, at pH 7.0 and 37°C
0.87
2-oxoglutarate
wild type enzyme, in potassium phosphate buffer, at pH 7.8 and 37°C
1
2-oxoglutarate
wild type enzyme, in potassium phosphate buffer, at pH 6.5 and 37°C
1.5
2-oxoglutarate
mutant enzyme R132H, in potassium phosphate buffer, at pH 7.5 and 37°C
0.01
DL-isocitrate
-
isoform ICD-1, presence of Mg2+, pH 7.5, 25°C
0.011
DL-isocitrate
Q8X277
mutant R291S/K343D/Y344I/V350A/Y390P, pH 8.0, 30°C
0.02
DL-isocitrate
-
isoform ICD-2, presence of Mg2+, pH 7.5, 25°C
0.021
DL-isocitrate
pH and temperature not specified in the publication
0.022
DL-isocitrate
-
isoform ICD-1, presence of Zn2+, pH 7.5, 25°C
0.054
DL-isocitrate
pH and temperature not specified in the publication
0.0062
isocitrate
-
recombinant wild-type IDH1, pH not specified in the publication, temperature not specified in the publication
0.027
isocitrate
wild type enzyme, in potassium phosphate buffer, at pH 6.2 and 37°C
0.034
isocitrate
wild type enzyme, in potassium phosphate buffer, at pH 6.5 and 37°C
0.04
isocitrate
wild type enzyme, in potassium phosphate buffer, at pH 6.8 and 37°C
0.042
isocitrate
wild type enzyme, in Bis-Tris buffer, at pH 6.2 and 37°C
0.048
isocitrate
wild type enzyme, in Bis-Tris buffer, at pH 6.5 and 37°C
0.05
isocitrate
pH 7.5, temperature not specified in the publication, recombinant His-tagged enzyme
0.05
isocitrate
wild type enzyme, in potassium phosphate buffer, at pH 7.0 and 37°C
0.0505
isocitrate
in the presence of Mn2+, pH and temperature not specified in the publication
0.0505
isocitrate
pH 8.0, 25°C, in presence of Mn2+, wild-type enzyme
0.06
isocitrate
wild type enzyme, in potassium phosphate buffer, at pH 7.2 and 37°C
0.061
isocitrate
wild type enzyme, in potassium phosphate buffer, at pH 7.5 and 37°C
0.0654
isocitrate
in the presence of Mg2+, pH and temperature not specified in the publication
0.0654
isocitrate
pH 8.0, 25°C, in presence of Mg2+, wild-type enzyme
0.066
isocitrate
wild type enzyme, in potassium phosphate buffer, at pH 7.8 and 37°C
0.067
isocitrate
wild type enzyme, in potassium phosphate buffer, at pH 8.0 and 37°C
0.075
isocitrate
wild type enzyme, in Bis-Tris buffer, at pH 7.0 and 37°C
0.1043
isocitrate
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S22A
0.1169
isocitrate
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S22H
0.1414
isocitrate
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S22E
0.15
isocitrate
mutant enzyme K217M, in potassium phosphate buffer, at pH 7.5 and 37°C
0.2447
isocitrate
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S113T
0.25
isocitrate
mutant enzyme K217Q, in potassium phosphate buffer, at pH 7.5 and 37°C
0.3276
isocitrate
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S113A
0.3686
isocitrate
-
recombinant mutant R132C IDH1, pH not specified in the publication, temperature not specified in the publication
0.4341
isocitrate
-
recombinant mutant R132S IDH1, pH not specified in the publication, temperature not specified in the publication
0.5824
isocitrate
-
recombinant mutant R132H IDH1, pH not specified in the publication, temperature not specified in the publication
1.9
isocitrate
mutant enzyme D273L, in potassium phosphate buffer, at pH 7.5 and 37°C
2.525
isocitrate
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S113G
12
isocitrate
mutant enzyme D273S, in potassium phosphate buffer, at pH 7.5 and 37°C
19
isocitrate
mutant enzyme D273N, in potassium phosphate buffer, at pH 7.5 and 37°C
0.13
NAD+
pH 8.0, 25°C, recombinant mutant D253A/S257K/K260Q/R314D/H315I/T327A
2.62
NAD+
mutant enzyme H590L/R601D, in the presence of Mn2+, at pH 8.2 and 45°C
3.474
NAD+
mutant enzyme H590L/R601D/R650S, in the presence of Mn2+, at pH 8.2 and 45°C
3.58
NAD+
pH 8.0, 25°C, recombinant wild-type enzyme
8.49
NAD+
in 20 mM Tris-HCl (pH 8.0), at 25°C, in the presence of 2 mM Mn2+
18.6
NAD+
in 20 mM Tris-HCl (pH 8.0), at 25°C, in the presence of 2 mM Mg2+
0.00242
NADP+
in 20 mM Tris-HCl (pH 8.0), at 25°C, in the presence of 2 mM Mg2+
0.00278
NADP+
in 20 mM Tris-HCl (pH 8.0), at 25°C, in the presence of 2 mM Mn2+
0.0068
NADP+
-
recombinant mutant R132C IDH1, pH not specified in the publication, temperature not specified in the publication
0.0073
NADP+
-
recombinant wild-type IDH1, pH not specified in the publication, temperature not specified in the publication
0.0122
NADP+
-
recombinant mutant R132H IDH1, pH not specified in the publication, temperature not specified in the publication
0.0144
NADP+
-
recombinant mutant R132S IDH1, pH not specified in the publication, temperature not specified in the publication
0.015
NADP+
pH 7.5, temperature not specified in the publication, recombinant His-tagged enzyme
0.0168
NADP+
wild type enzyme, in the presence of Mn2+, at pH 8.2 and 45°C
0.0181
NADP+
in the presence of Mg2+, pH and temperature not specified in the publication
0.0181
NADP+
pH 8.0, 25°C, in presence of Mg2+, wild-type enzyme
0.01945
NADP+
pH 8.0, 25°C, recombinant wild-type enzyme
0.0223
NADP+
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S22H
0.0261
NADP+
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S22A
0.0289
NADP+
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S22E
0.045
NADP+
pH and temperature not specified in the publication
0.0466
NADP+
in the presence of Mn2+, pH and temperature not specified in the publication
0.0466
NADP+
pH 8.0, 25°C, in presence of Mn2+, wild-type enzyme
0.0552
NADP+
pH 8.0, 70°C, Km-value for NAD+ is about 140fold higher than the KM-value for NADP+
0.056
NADP+
pH and temperature not specified in the publication
0.0879
NADP+
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S113T
0.1221
NADP+
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S113A
0.324
NADP+
pH 8.0, 25°C, recombinant mutant D253A/S257K/K260Q/R314D/H315I/T327A
0.4868
NADP+
mutant enzyme H590L/R601D, in the presence of Mn2+, at pH 8.2 and 45°C
0.8546
NADP+
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S113G
10.457
NADP+
mutant enzyme H590L/R601D/R650S, in the presence of Mn2+, at pH 8.2 and 45°C
0.0025
NADPH
Km less than 0.0025 mM or equal, mutant enzyme R100Q, at pH 7.5 and 21°C
0.005
NADPH
Km less than 0.005 mM or equal, mutant enzyme R132H, at pH 7.5 and 21°C
0.01
NADPH
Km less than 0.01 mM or equal, wild type enzyme, at pH 7.5 and 37°C
0.025
NADPH
Km less than 0.025 mM or equal, mutant enzyme R132C, at pH 7.5 and 21°C
0.025
NADPH
Km less than 0.025 mM or equal, mutant enzyme R132G, at pH 7.5 and 21°C
0.025
NADPH
Km less than 0.025 mM or equal, mutant enzyme R132H, at pH 7.5 and 37°C
0.025
NADPH
Km less than 0.025 mM, mutant enzyme R132G, at pH 7.5 and 37°C
additional information
additional information
kinetic analysis
-
additional information
additional information
-
kinetics of isozymes IDP1 and IDP2
-
additional information
additional information
-
measurement methods, the maltose binding fusion protein of the recombinant enzymes alters the kinetic parameters, overview
-
additional information
additional information
kinetics analysis, overview
-
additional information
additional information
Km-values of wild-type and chimeric enzymes
-
additional information
additional information
-
Km-values of wild-type and chimeric enzymes
-
additional information
additional information
Km-values of wild-type and chimeric enzymes
-
additional information
additional information
-
Km-values of wild-type and chimeric enzymes
-
additional information
additional information
steady-state kinetics, kinetic mechanism of ICDH-1, overview
-
additional information
additional information
-
steady-state kinetics, kinetic mechanism of ICDH-1, overview
-
additional information
additional information
stopped-flow kinetics and steady-state kientics
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.016
2-oxoglutarate
kcat less than 0.016 s-1 or equal, mutant enzyme H133Q, at pH 7.5 and 37°C
0.019
2-oxoglutarate
kcat less than 0.019 s-1 or equal, mutant enzyme A134D, at pH 7.5 and 37°C
1.44
2-oxoglutarate
mutant enzyme R132H, in potassium phosphate buffer, at pH 7.5 and 37°C
1.6
2-oxoglutarate
wild type enzyme, in Bis-Tris buffer, at pH 6.2 and 37°C
1.87
2-oxoglutarate
wild type enzyme, in potassium phosphate buffer, at pH 7.8 and 37°C
3.2
2-oxoglutarate
wild type enzyme, in Bis-Tris buffer, at pH 6.5 and 37°C
3.3
2-oxoglutarate
wild type enzyme, in Bis-Tris buffer, at pH 6.8 and 37°C
3.5
2-oxoglutarate
wild type enzyme, in potassium phosphate buffer, at pH 6.2 and 37°C
3.8
2-oxoglutarate
wild type enzyme, in Bis-Tris buffer, at pH 7.0 and 37°C
3.8
2-oxoglutarate
wild type enzyme, in potassium phosphate buffer, at pH 7.5 and 37°C
3.87
2-oxoglutarate
wild type enzyme, in potassium phosphate buffer, at pH 7.2 and 37°C
4.1
2-oxoglutarate
wild type enzyme, in potassium phosphate buffer, at pH 6.5 and 37°C
4.1
2-oxoglutarate
wild type enzyme, in potassium phosphate buffer, at pH 7.0 and 37°C
4.9
2-oxoglutarate
wild type enzyme, in potassium phosphate buffer, at pH 6.8 and 37°C
0.005
DL-isocitrate
Q8X277
mutant R291S/K343D/Y344I/V350A/Y390P, pH 8.0, 30°C
19.6
DL-isocitrate
-
isoform ICD-2, presence of Mg2+, pH 7.5, 25°C
2.1
isocitrate
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S113A
3 - 6
isocitrate
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S22E
3.2
isocitrate
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S113T
4
isocitrate
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S113G
7
isocitrate
mutant enzyme D273L, in potassium phosphate buffer, at pH 7.5 and 37°C
15
isocitrate
mutant enzyme D273S, in potassium phosphate buffer, at pH 7.5 and 37°C
20.2
isocitrate
wild type enzyme, in potassium phosphate buffer, at pH 6.2 and 37°C
22
isocitrate
mutant enzyme D273N, in potassium phosphate buffer, at pH 7.5 and 37°C
23
isocitrate
wild type enzyme, in potassium phosphate buffer, at pH 6.5 and 37°C
27.5
isocitrate
wild type enzyme, in potassium phosphate buffer, at pH 6.8 and 37°C
28.7
isocitrate
mutant enzyme K217Q, in potassium phosphate buffer, at pH 7.5 and 37°C
31.3
isocitrate
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S22A
31.7
isocitrate
wild type enzyme, in potassium phosphate buffer, at pH 7.0 and 37°C
33
isocitrate
pH 7.5, temperature not specified in the publication, recombinant His-tagged enzyme
33.4
isocitrate
pH 8.0, 25°C, in presence of Mg2+, wild-type enzyme
35.5
isocitrate
wild type enzyme, in potassium phosphate buffer, at pH 7.2 and 37°C
37
isocitrate
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S22H
37.6
isocitrate
wild type enzyme, in potassium phosphate buffer, at pH 7.5 and 37°C
39.2
isocitrate
wild type enzyme, in potassium phosphate buffer, at pH 8.0 and 37°C
40
isocitrate
wild type enzyme, in potassium phosphate buffer, at pH 7.8 and 37°C
42
isocitrate
mutant enzyme K217M, in potassium phosphate buffer, at pH 7.5 and 37°C
50.4
isocitrate
pH 8.0, 25°C, in presence of Mn2+, wild-type enzyme
0.518
NAD+
pH 8.0, 25°C, recombinant mutant D253A/S257K/K260Q/R314D/H315I/T327A
1.37
NAD+
in 20 mM Tris-HCl (pH 8.0), at 25°C, in the presence of 2 mM Mn2+
2.11
NAD+
in 20 mM Tris-HCl (pH 8.0), at 25°C, in the presence of 2 mM Mg2+
11.7
NAD+
pH 8.0, 25°C, recombinant wild-type enzyme
52.3
NAD+
mutant enzyme H590L/R601D, in the presence of Mn2+, at pH 8.2 and 45°C
113.9
NAD+
mutant enzyme H590L/R601D/R650S, in the presence of Mn2+, at pH 8.2 and 45°C
0.307
NADP+
pH 8.0, 25°C, recombinant mutant D253A/S257K/K260Q/R314D/H315I/T327A
2
NADP+
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S113A
2.9
NADP+
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S113T
3.4
NADP+
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S113G
23.2
NADP+
in 20 mM Tris-HCl (pH 8.0), at 25°C, in the presence of 2 mM Mg2+
27.6
NADP+
in 20 mM Tris-HCl (pH 8.0), at 25°C, in the presence of 2 mM Mn2+
28.5
NADP+
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S22A
29.2
NADP+
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S22H
29.8
NADP+
pH 8.0, 25°C, in presence of Mg2+, wild-type enzyme
30.3
NADP+
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S22E
33
NADP+
pH 7.5, temperature not specified in the publication, recombinant His-tagged enzyme
36.4
NADP+
pH 8.0, 25°C, recombinant wild-type enzyme
53.1
NADP+
mutant enzyme H590L/R601D, in the presence of Mn2+, at pH 8.2 and 45°C
55.5
NADP+
wild type enzyme, in the presence of Mn2+, at pH 8.2 and 45°C
57.9
NADP+
mutant enzyme H590L/R601D/R650S, in the presence of Mn2+, at pH 8.2 and 45°C
60.1
NADP+
pH 8.0, 25°C, in presence of Mn2+, wild-type enzyme
additional information
additional information
turnover numbers of wild-type and chimeric enzymes
-
additional information
additional information
-
turnover numbers of wild-type and chimeric enzymes
-
additional information
additional information
turnover numbers of wild-type and chimeric enzymes
-
additional information
additional information
-
turnover numbers of wild-type and chimeric enzymes
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1
2-oxoglutarate
mutant enzyme R132H, in potassium phosphate buffer, at pH 7.5 and 37°C
2.1
2-oxoglutarate
wild type enzyme, in potassium phosphate buffer, at pH 7.8 and 37°C
4.1
2-oxoglutarate
wild type enzyme, in potassium phosphate buffer, at pH 6.5 and 37°C
5.8
2-oxoglutarate
wild type enzyme, in potassium phosphate buffer, at pH 7.0 and 37°C
6
2-oxoglutarate
wild type enzyme, in potassium phosphate buffer, at pH 6.2 and 37°C
7.5
2-oxoglutarate
wild type enzyme, in potassium phosphate buffer, at pH 6.8 and 37°C
8.3
2-oxoglutarate
wild type enzyme, in potassium phosphate buffer, at pH 7.5 and 37°C
14
2-oxoglutarate
wild type enzyme, in potassium phosphate buffer, at pH 7.2 and 37°C
24
2-oxoglutarate
wild type enzyme, in Bis-Tris buffer, at pH 6.8 and 37°C
27
2-oxoglutarate
wild type enzyme, in Bis-Tris buffer, at pH 6.5 and 37°C
27
2-oxoglutarate
wild type enzyme, in Bis-Tris buffer, at pH 7.0 and 37°C
40
2-oxoglutarate
wild type enzyme, in Bis-Tris buffer, at pH 6.2 and 37°C
1.2
isocitrate
mutant enzyme D273N, in potassium phosphate buffer, at pH 7.5 and 37°C
1.3
isocitrate
mutant enzyme D273S, in potassium phosphate buffer, at pH 7.5 and 37°C
2
isocitrate
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S113G
3.7
isocitrate
mutant enzyme D273L, in potassium phosphate buffer, at pH 7.5 and 37°C
6
isocitrate
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S113A
13
isocitrate
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S113T
115
isocitrate
mutant enzyme K217Q, in potassium phosphate buffer, at pH 7.5 and 37°C
250
isocitrate
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S22E
280
isocitrate
mutant enzyme K217M, in potassium phosphate buffer, at pH 7.5 and 37°C
300
isocitrate
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S22A
320
isocitrate
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S22H
500
isocitrate
pH 8.0, 25°C, in presence of Mg2+, wild-type enzyme
590
isocitrate
wild type enzyme, in potassium phosphate buffer, at pH 7.2 and 37°C
590
isocitrate
wild type enzyme, in potassium phosphate buffer, at pH 8.0 and 37°C
610
isocitrate
wild type enzyme, in potassium phosphate buffer, at pH 7.8 and 37°C
620
isocitrate
wild type enzyme, in potassium phosphate buffer, at pH 7.5 and 37°C
630
isocitrate
wild type enzyme, in potassium phosphate buffer, at pH 7.0 and 37°C
680
isocitrate
wild type enzyme, in potassium phosphate buffer, at pH 6.5 and 37°C
690
isocitrate
wild type enzyme, in potassium phosphate buffer, at pH 6.8 and 37°C
750
isocitrate
wild type enzyme, in potassium phosphate buffer, at pH 6.2 and 37°C
1000
isocitrate
pH 8.0, 25°C, in presence of Mn2+, wild-type enzyme
0.01996
NAD+
mutant enzyme H590L/R601D, in the presence of Mn2+, at pH 8.2 and 45°C
0.03278
NAD+
mutant enzyme H590L/R601D/R650S, in the presence of Mn2+, at pH 8.2 and 45°C
0.95
NAD+
pH 8.0, 25°C, recombinant mutant D253A/S257K/K260Q/R314D/H315I/T327A
3
NAD+
pH 8.0, 25°C, recombinant wild-type enzyme
4
NAD+
pH 8.0, 25°C, recombinant mutant D253A/S257K/K260Q/R314D/H315I/T327A
1870
NAD+
pH 8.0, 25°C, recombinant wild-type enzyme
0.00553
NADP+
mutant enzyme H590L/R601D/R650S, in the presence of Mn2+, at pH 8.2 and 45°C
0.109
NADP+
mutant enzyme H590L/R601D, in the presence of Mn2+, at pH 8.2 and 45°C
1.1
NADP+
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S22A
1.3
NADP+
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S22H
3.303
NADP+
wild type enzyme, in the presence of Mn2+, at pH 8.2 and 45°C
4
NADP+
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S113G
16
NADP+
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S113A
33
NADP+
pH 8.0, 25°C, in presence of Mg2+, mutant enzyme S113T
1300
NADP+
pH 8.0, 25°C, in presence of Mn2+, wild-type enzyme
1700
NADP+
pH 8.0, 25°C, in presence of Mg2+, wild-type enzyme
additional information
additional information
turnover numbers of wild-type and chimeric enzymes
-
additional information
additional information
-
turnover numbers of wild-type and chimeric enzymes
-
additional information
additional information
turnover numbers of wild-type and chimeric enzymes
-
additional information
additional information
-
turnover numbers of wild-type and chimeric enzymes
-
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00021
(5aS,6S,9aR)-2-benzoyl-6-methyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile
Homo sapiens
pH and temperature not specified in the publication
0.01
(5aS,6S,9aR)-6-methyl-7-oxo-9a-phenyl-4,5,5a,6,7,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile
Homo sapiens
IC50 above 0.01 mM, pH and temperature not specified in the publication
0.00011 - 0.00177
(6aS,7S,10aR)-2-anilino-7-methyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile
0.00041
(6aS,7S,10aR)-7,10a-dimethyl-8-oxo-2-(phenylamino)-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile
Homo sapiens
pH and temperature not specified in the publication
0.000082
(6aS,7S,10aR)-7-methyl-8-oxo-10a-phenyl-2-[(pyridin-3-yl)amino]-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile
Homo sapiens
pH and temperature not specified in the publication
0.008
(6aS,7S,10aR)-7-methyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile
Homo sapiens
pH and temperature not specified in the publication
0.01
(6aS,7S,10aS)-2-anilino-7-methyl-10a-phenyl-5,6a,7,10a-tetrahydrobenzo[h]quinazolin-8(6H)-one
Homo sapiens
IC50 above 0.01 mM, pH and temperature not specified in the publication
0.00012
(7R)-1-[(4-fluorophenyl)methyl]-N-[3-[(1R)-1-hydroxyethyl]phenyl]-7-methyl-5-(1H-pyrrole-2-carbonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-3-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.0015
3-[(5aS,6S,9aR)-8-cyano-6-methyl-7-oxo-2,4,5,5a,6,7-hexahydro-9aH-benzo[g]indazol-9a-yl]benzoic acid
Homo sapiens
pH and temperature not specified in the publication
0.000041
3-[(6aS,7S,10aR)-2-anilino-9-cyano-7-methyl-8-oxo-6,6a,7,8-tetrahydrobenzo[h]quinazolin-10a(5H)-yl]benzoic acid
Homo sapiens
pH and temperature not specified in the publication
0.00027
4,5,6,7-tetrabromo-1,3-dihydro-2H-benzimidazol-2-one
Homo sapiens
pH and temperature not specified in the publication
0.00011
(6aS,7S,10aR)-2-anilino-7-methyl-8-oxo-10a-phenyl-5,6,6a,7,8,10a-hexahydrobenzo[h]quinazoline-9-carbonitrile
Homo sapiens
pH and temperature not specified in the publication
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.01
0.038
0.04
0.06
0.75
-
cell free enzyme extracts of cells grown on glucose, best carbon source
18.6
219
purified recombinant N-terminally His6-tagged enzyme, pH and temperature not specified in the publication
35.1
50
67
purified recombinant N-terminally His6-tagged enzyme, pH and temperature not specified in the publication
additional information
additional information
-
activity in cell free enzyme extracts of cells grown on diffeent carbon sources
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.2
7.3
7.4
7.5
7.8
8.2
8.5
7.5
the recombinant MaIDH has a broader pH optimum from pH 6.5 to pH 8.5
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5 - 8
5.5
-
isoform ICD-1, 30% of maximum activity, isoform ICD-2, 10% of maximum activity
5.8 - 7.5
three-fold reduction in activity when the pH is shifted from the pH-optimum at 7.5 to pH 5.8
6 - 9.5
6.5 - 10
6.5 - 9
7 - 8
pH 7.0: about 60% of maximal activity, pH 8.0: about 40% of maximal activity, isoenzyme IDP2
7 - 9
pH 7.0: about 60% of maximal activity, pH 9.0: about 95% of maximal activity, isoenzyme IDP1
7.6 - 8.8
-
measurements below pH 7.6 and above pH 8.8 lead to activities lower than 50% of its Vmax value
9.5
-
isoform ICD-1, 90% of maximum activity, isoform ICD-2, less than 40% of maximum activity
additional information
6.5 - 9
pH 6.5: about 60% of maximal activity, pH 9.0: about 70% of maximal activity, isoenzyme IDP1
6.5 - 9
pH 6.5: about 40% of maximal activity, pH 9.0: about 70% of maximal activity, isoenzyme IDP3
additional information
pH-profile, recombinant wild-type and mutant enzymes
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
20
22
25
28
30
37
40
45
50
55
60
65
70
75
90
50
optimum of the IDH overall activity in Colwellia psychrerythraea crude cell extract
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
10 - 60
activity range of the IDH overall activity in Colwellia psychrerythraea crude cell extract, inactivation above
25 - 50
25°C: about 50% of maximal activity, 50°C: about 70% of maximal activity, enzyme from ischemic heart
25 - 55
-
temperature dependency analysis of the different phenotypes
35 - 70
35°C: about 45% of maximal activity, 70°C: about 60% of maximal activity, enzyme from normoxic heart
50 - 80
50°C: about 50% of maximal activity, 80°C: about 65% of maximal activity
60
-
isoform ICD-1, 40% residual activity, ICD-2, 5% residual activity
additional information
additional information
isozyme IDH-IIa is a cold-adapted enzyme
additional information
isozyme IDH-IIa is a cold-adapted enzyme
additional information
isozyme IDH-IIa is a mesophilic enzyme
additional information
isozyme IDH-IIa is a mesophilic enzyme
additional information
isozyme IDH-IIb is a cold-adapted enzyme
additional information
isozyme IDH-IIb is a cold-adapted enzyme
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4.9
5.2
5.5
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
from 3 different altitudes of a stream of 700-1920 m, 2 polymorphic isozymes IDHP-A and IDHP-B, isozymes show allelic variants in populations belonging to different living heights in the stream, overview
-
-
brenda
both mitochondrial and cytosolic isoform, expression in human fibroblast. Inverse relationship between the amount of enzyme expressed in target cells and their susceptibility to senescence as shown by changes in replicative potential, cell cycle, expression of p21 and p53. Lipid peroxidation, oxidative DNA damage, and intracellular peroxide generation is higher and cellular redox status shifts to a prooxidant condition in cells expressing low levels of enzyme
-
-
brenda
HL-60 cell lines with stable transfections with the cDNA for mouse IDPc
-
-
brenda
cv. 294 040 Märgärt Kelvedon Wonder, one cytosolic and one mitochondrial isozyme
-
-
brenda
cytosolic isozyme; 1 cytosolic and 1 mitochondrial isozyme
SwissProt
brenda
3 isozymes: mitochondrial IDP1, cytosolic IDP2, peroxisomal IDP3
-
-
brenda
gene Tc00.1047053506925.319 or IDH2; gene idh, two isozymes
UniProt
brenda
gene Tc00.1047053511575.60 or IDH1; gene idh, isozyme IDH1
UniProt
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
pancreatic islet beta-cell, suppression of enzyme activity by small interfering RNA results in impairment of glucose-stimulated insulin secretion, attenuates glucose-induced increments in pyruvate cycling activity and in NADPH levels, and causes increases in lactate production
brenda
a remarkable induction of ICDH gene expression and a dramatic increase of the ICDH activity is observed during the paraquat treatment. ICDH has a key role in NADPH recycling under oxidative stress conditions in pea root nodules
brenda
mainly localized to the principal piece of the porcine sperm flagellum
brenda
additional information
regulation of enzyme during heart ischemia. Ischemia results in increase in enzyme activity, enzyme from ischemic heart mitochondria demonstrates higher activation energy and lower thermal stability and differs in KM-value and regulation
brenda
increase of enzyme activity in the cytosol and mitochondria of ischemic heart
brenda
-
sensitizing effect of IDPm siRNA on the apoptotic cell death of HeLa cells
brenda
silencing of NADP+-dependent isocitrate dehydrogenase expression in HeLa cells greatly enhances apoptosis induced by heat shock
brenda
-
IDPc expression and activity is highest in the cortex, modest in the outer medulla and lowest in the inner medulla, IDPc is also highly expressed in the mitochondrion-rich intercalatal cells of the collecting duct
brenda
NADP+-dependent isocitrate dehydrogenase may play an important role in regulating the apoptosis induced by ionizing radiation
brenda
additional information
-
isozyme tissue distribution of isozyme ICD1, overview
brenda
additional information
RT-PCR and immunohistochemical analysis of brain cells, overview
brenda
additional information
-
growth-associated specific activity profile, dextrose or fructose are preferred before lactose as sole carbon source
brenda
additional information
-
growth-associated specific activity profile, dextrose or fructose are preferred before lactose as sole carbon source
-
brenda
additional information
expression levels of the cytosolic isoform are significantly increased in amastigotes, metacyclic trypomastigotes and cell-derived trypomastigotes compared to epimastigotes
brenda
additional information
expression levels of the cytosolic isoform are significantly increased in amastigotes, metacyclic trypomastigotes and cell-derived trypomastigotes compared to epimastigotes
brenda
additional information
-
expression levels of the cytosolic isoform are significantly increased in amastigotes, metacyclic trypomastigotes and cell-derived trypomastigotes compared to epimastigotes
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
IDH2 contains a C-terminal PTS1 signal, but this enzyme is mostly localized in the cytosol of epimastigotes
brenda
additional information
-
86% of total activity in the cell, main factor for synthesis of 2-oxoglutarate. Enzyme and cytoplasmic aspartate aminotransferase are regulated oppositely and the catalytic activity of one enzyme can be stimulated concurrently with a decrease in the activity of the other
brenda
-
cytosolic isozyme IDPc, subcellular localization study, overview
brenda
-
IDP2 carrying a type I peroxisomal targeting sequence, IDP2+CKL, is only partially localized to peroxisomes, the enzyme is able to function either instead of peroxisomal IDP3 or as cytosolic IDP2
brenda
-
IDP2 carrying a type I peroxisomal targeting sequence, IDP2+CKL, is only partially localized to peroxisomes, the enzyme is able to function either instead of peroxisomal IDP3 or as cytosolic IDP2
-
brenda
IDH2 contains a C-terminal PTS1 signal, but this enzyme is mostly localized in the cytosol, expression levels of the cytosolic isoform are significantly increased in amastigotes, metacyclic trypomastigotes and cell-derived trypomastigotes compared to epimastigotes
brenda
-
mitochondrial NADP+-dependent isocitrate dehydrogenase
brenda
increase in enzyme activity during ischemia, enzyme from ischemic heart mitochondria demonstrates higher activation energy and lower thermal stability and differs in KM-value and regulation
brenda
mitochondrial targeting peptide signal is predicted for IDH1
brenda
-
IDP3 contains a canonical type I peroxisomal targeting sequence, a carboxyl-terminal Cys-Lys-Leu tripeptide. IDP3 is normally strictly peroxisomal
brenda
-
IDP3 contains a canonical type I peroxisomal targeting sequence, a carboxyl-terminal Cys-Lys-Leu tripeptide. IDP3 is normally strictly peroxisomal
-
brenda
additional information
the mouse isoenzyme IDP2 colocalizes in cytosol and peroxisomes when expressed in yeast
-
brenda
additional information
the mouse isoenzyme IDP2 colocalizes in cytosol and peroxisomes when expressed in yeast
-
brenda
additional information
-
the mouse isoenzyme IDP2 colocalizes in cytosol and peroxisomes when expressed in yeast
-
brenda
additional information
-
immunohistochemical determination of the subcellular distribution of isozyme ICD1 in different tissues, overview
-
brenda
additional information
subcellular RT-PCR and immunohistochemical analysis of brain cells, overview
-
brenda
additional information
-
influence of subcellular localization on isozyme activities, overview
-
brenda
additional information
-
subcellular localization study of isozymes, overview
-
brenda
additional information
-
subcellular localization study of isozymes, overview
-
-
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
evolution
Arabidopsis thaliana has three NADP-ICDH genes At1g65930, At5g14590, and At1g54340, coding for the proteins NP_176768, NP_196963, and BT025983, respectively, that are located in different subcellular compartments, i.e. cytosol, chloroplasts, mitochondria, and peroxisomes
evolution
based on the phylogenetic analysis, IDHs can be divided into three subfamilies: Type I IDHs, Type II IDHs and monomeric IDHs. The enzyme BlIDH from Bifidobacterium longum belongs to the type II subfamily. NAD+ use is an ancestral trait and NADP+ use by bacterial IDHs arose on or about the time that eukaryotic mitochondria first appeared, some 3.5 billion years ago
evolution
phylogenetic analysis and evolutionary relationships between YlIDP and IDPs from other yeasts or yeast-related species
evolution
the overall fold of the enzyme protein is resolved into large domain, small domain and a clasp domain. The monomeric structure reveals also a terminal domain involved in dimerization, a very unique domain when compared to other IDHs. The small domain and clasp domain show significant differences when compared to other IDHs of the same subfamily. The structure of TtIDH reveals the absence of helix at the clasp domain, which is mainly involved in oligomerization in other IDHs. Also, helices/beta sheets are absent in the small domain, when compared to other IDHs of the same subfamily. The overall TtIDH structure exhibits a closed conformation with the conserved catalytic triad residues Tyr144, Asp248, and Lys191. Oligomerization of the protein is determined using interface area and subunitsubunit interactions between protomers. The TtIDH structure with the terminal domain may be categorized as a first structure of a type IV subfamily
evolution
three NADP+-dependent isocitrate dehydrogenase (IDH) isozymes of a psychrophilic bacterium, Colwellia psychrerythraea strain 34H, are analyzed: two monomeric (IDH-IIa and IDH-IIb) and one dimeric (IDH-I) IDHs
evolution
-
phylogenetic analysis and evolutionary relationships between YlIDP and IDPs from other yeasts or yeast-related species
-
evolution
-
Arabidopsis thaliana has three NADP-ICDH genes At1g65930, At5g14590, and At1g54340, coding for the proteins NP_176768, NP_196963, and BT025983, respectively, that are located in different subcellular compartments, i.e. cytosol, chloroplasts, mitochondria, and peroxisomes
-
evolution
-
three NADP+-dependent isocitrate dehydrogenase (IDH) isozymes of a psychrophilic bacterium, Colwellia psychrerythraea strain 34H, are analyzed: two monomeric (IDH-IIa and IDH-IIb) and one dimeric (IDH-I) IDHs
-
evolution
-
based on the phylogenetic analysis, IDHs can be divided into three subfamilies: Type I IDHs, Type II IDHs and monomeric IDHs. The enzyme BlIDH from Bifidobacterium longum belongs to the type II subfamily. NAD+ use is an ancestral trait and NADP+ use by bacterial IDHs arose on or about the time that eukaryotic mitochondria first appeared, some 3.5 billion years ago
-
malfunction
autophagic response to ionizing radiation in A-172 glioma cells transfected with small interfering RNA (siRNA) targeting the IDPm gene. Autophagy in A-172 transfectant cells is associated with enhanced autophagolysosome formation and GFP-LC3 punctuation/aggregation. The inhibition of autophagy by chloroquine augments apoptotic cell death of irradiated A-172 cells transfected with IDPm siRNA. The activity of cytosolic NADP+-dependent isocitrate dehydrogenase (IDPc) is not affected by the transfection of IDPm siRNA. The decreased activity caused by knockdown of IDPm siRNA is also observed in U87MG glioma cell line. When cultured A172 cells are treated with gamma-radiation, an increase in cell death is observed, but A172 cells transfected with IDPm siRNA are significantly more sensitive than control cells in this respect
malfunction
mitochondrial NADP+-dependent isocitrate dehydrogenase deficiency exacerbates mitochondrial and cell damage after kidney ischemia-reperfusion injury, Idh2 gene deletion exacerbates ROS production and oxidative stress after ischemia-reperfusion, and causes I/R-induced mitochondrial dysfunction and morphologic fragmentation, resulting in severe apoptosis in kidney tubule cells, it impairs reduction of NADP+ and GSSG within mitochondria
malfunction
transfection of H9c2 clonal myoblastic cells with small interfering RNA (siRNA) specific for IDPm markedly attenuates IDPm expression and substantially induces apoptosis, senescence, and hypertrophy as indicated by increased atrial natriuretic peptide gene expression, a marker of cardiomyocyte hypertrophy, and a larger cell size. Knockdown of IDPm expression results in the modulation of cellular and mitochondrial redox status, mitochondrial function, and cellular oxidative damage. The suppression of IDP expression by siRNA induces apoptosis and hypertrophy of cultured cardiomyocytes through the disruption of cellular redox balance. IDPm knockdown alters cellular redox status and induces oxidative damage. Apoptosis induced by IDPm knockdown is ROS-mediated. Substantially increased desmin and vimentin abundance is observed in IDPm siRNA-transfected H9c2 cells compared to the control cells. Mitochondrial fission and fusion involve enzymatic reactions mediated by large dynamin-associated GTPases. IDPm knockdown induces mitochondrial damage by altering the redox status
malfunction
two mutant forms (R132H and R132C) of isocitrate dehydrogenase 1 (IDH1) have been associated with a number of cancers including glioblastoma and acute myeloid leukemia. These mutations confer a neomorphic activity of 2-hydroxyglutarate (2-HG) production, and 2-HG has previously been implicated as an oncometabolite. Inhibitors of mutant IDH1 can potentially be used to treat these diseases
malfunction
enzyme deficiency increases cisplatin-induced oxidative damage in kidney tubule cells, inducing more severe nephrotoxicity
malfunction
enzyme knockout mice are more susceptible to high fat diet-induced obesity than wild type mice.Brown adipose tissue dysfunction in the enzyme knockout mice is due to mitochondrial dysfunction
malfunction
-
mitochondrial NADP+-dependent isocitrate dehydrogenase deficiency exacerbates mitochondrial and cell damage after kidney ischemia-reperfusion injury, Idh2 gene deletion exacerbates ROS production and oxidative stress after ischemia-reperfusion, and causes I/R-induced mitochondrial dysfunction and morphologic fragmentation, resulting in severe apoptosis in kidney tubule cells, it impairs reduction of NADP+ and GSSG within mitochondria
-
metabolism
metabolite profiling identifies elevated 2-hydroxyglutarate levels in IDH1 mutant R132H expressing cells compared to wild-type
metabolism
-
NAD(P)+-dependent isocitrate dehydrogenase is a key enzyme in tricarboxylic acid cycle
metabolism
NADP-isocitrate dehydrogenase catalyses the first oxidative decarboxylation reaction of the tricarboxic acid cycle, yielding 2-oxoglutarate, CO2, and NADPH from isocitrate via a two-step reaction
metabolism
-
in the tricarboxylic acid cycle, NADP+-specific isocitrate dehydrogenase catalyzes oxidative decarboxylation of isocitric acid to form 2-oxoglutaric acid with NADP+ as a cofactor. NADP+-ICDH may work independently of NAD+-ICDH, EC 1.1.1.41, as one of the TCA cycle regulatory enzymes, especially in relation to citric acid production by Aspergillus niger
metabolism
the enzyme catalyzes an essential rate-limiting step in the citric acid cycle
metabolism
-
NAD(P)+-dependent isocitrate dehydrogenase is a key enzyme in tricarboxylic acid cycle
-
metabolism
-
NADP-isocitrate dehydrogenase catalyses the first oxidative decarboxylation reaction of the tricarboxic acid cycle, yielding 2-oxoglutarate, CO2, and NADPH from isocitrate via a two-step reaction
-
physiological function
-
cICDH is involved in amino acid synthesis, and plays a role in redox signalling linked to pathogen responses, but cICDH is not required for plant development and primary metabolism in optimal growth conditions
physiological function
elective pressures in the brain environment may specifically favor the cell growth or survival of tumor cells with mutations in IDH1, regardless of primary tumor site
physiological function
elective pressures in the brain environment may specifically favor the cell growth or survival of tumor cells with mutations in IDH2, regardless of primary tumor site
physiological function
-
IDH1 mutation predicts outcome in grade 2, 3, and 4 gliomas
physiological function
-
IDH1 regulates HIF-1alpha levels by controlling the level of 2-oxoglutarate. IDH1 appears to function as a tumor suppressor that, when mutationally inactivated, contributes to tumorigenesis in part through induction of the HIF-1 pathway. IDH1 is likely to function as a tumor suppressor gene rather than as an oncogene
physiological function
-
IDP3 provides the NADPH required for beta-oxidation of some fatty acids in the peroxisome
physiological function
mutation at R172 in the active site of IDH2 leads to a change in the molecular mechanism of enzyme catalysis, resulting in production and accumulation of elevated 2-hydroxyglutarate in acute myelogenous leukemia. The mutation reduces the affinity for isocitrate, and increases the affinity for NADPH and 2-oxoglutarate, preventing the oxidative decarboxylation of isocitrate to 2-oxoglutarate, and facilitating the conversion of 2-oxoglutarate to 2-hydroxyglutarate
physiological function
mutations at R132 in the active site of IDH1 lead to a change in the molecular mechanism of enzyme catalysis, resulting in production and accumulation of elevated 2-hydroxyglutarate in acute myelogenous leukemia. The mutations reduce the affinity for isocitrate, and increase the affinity for NADPH and 2-oxoglutarate, preventing the oxidative decarboxylation of isocitrate to 2-oxoglutarate, and facilitating the conversion of 2-oxoglutarate to 2-hydroxyglutarate
physiological function
-
the mitochondrial NADP+-dependent isocitrate dehydrogenase controls the mitochondrial redox balance by supplying NADPH for antioxidant systems
physiological function
-
in the cytoplasm, NADP+-IDH often contributes significantly to the NADPH pool required for reductive fatty acid biosynthesis
physiological function
isocitrate dehydrogenase plays pivotal role in the growth and pathogenesis of the bacteria
physiological function
isocitrate dehydrogenase of Microcystis aeruginosa plays important roles in energy and biosynthesis metabolisms and its catalytic product 2-oxoglutarate provides the carbon skeleton for ammonium assimilation and also constitutes a signaling molecule of nitrogen starvation in cyanobacteria
physiological function
-
membranes in cardiolipin-modified liposomes are dehydrated by ICDH binding. Liposomes induce a conformational change in ICDH, indicating that cardiolipin-rich membrane domains can inhibit ICDH activity. Lipid membranes, including cardiolipin molecules, can act as a platform to regulate ICDH-related metabolic pathways such as the tricarboxylic acid cycle and lipid synthesis
physiological function
mitochondrial NADP+-dependent isocitrate dehydrogenase (IDH2) catalyzes the oxidative decarboxylation of isocitrate to 2-oxooglutarate, synthesizing NADPH, which is essential for mitochondrial redox balance
physiological function
mitochondrial NADP+s-dependent isocitrate dehydrogenase (IDPm) functions as an antioxidant and antiapoptotic protein by supplying NADPH to antioxidant systems
physiological function
NADP+-dependent IDH generates NADPH, which provides the reducing power for biosynthesis, maintains the redox state of the cell, and takes part in CO2 assimilation
physiological function
-
the cytosolic homodimeric isocitrate dehydrogenase (hICDH) is involved in the regulation of tumorogenesis
physiological function
the enzyme dictates the flow of carbon as part of the Krebs cycle thereby controlling the virulence and biofilm formation
physiological function
the enzyme dictates the flow of carbon as part of the Krebs cycle thereby controlling the virulence and biofilm formation
physiological function
enzyme-overexpressing transgenic poplars show an increased expression of glutamine synthetase, glutamate decarboxylase and other genes associated with vascular differentiation. Furthermore, these plants exhibit increased growth in height, longer internodes and enhanced vascular development in young leaves and the apical region of stem
physiological function
the enzyme is critical in the NADPH-associated mitochondrial antioxidant system and is involved in cisplatin nephrotoxicity. The mitochondrial enzyme-NADPH-glutathione antioxidant system is a target for the prevention of cisplatin-induced kidney cell death
physiological function
-
cICDH is involved in amino acid synthesis, and plays a role in redox signalling linked to pathogen responses, but cICDH is not required for plant development and primary metabolism in optimal growth conditions
-
physiological function
-
IDP3 provides the NADPH required for beta-oxidation of some fatty acids in the peroxisome
-
physiological function
-
mitochondrial NADP+-dependent isocitrate dehydrogenase (IDH2) catalyzes the oxidative decarboxylation of isocitrate to 2-oxooglutarate, synthesizing NADPH, which is essential for mitochondrial redox balance
-
physiological function
-
NADP+-dependent IDH generates NADPH, which provides the reducing power for biosynthesis, maintains the redox state of the cell, and takes part in CO2 assimilation
-
physiological function
-
isocitrate dehydrogenase plays pivotal role in the growth and pathogenesis of the bacteria
-
physiological function
-
the enzyme dictates the flow of carbon as part of the Krebs cycle thereby controlling the virulence and biofilm formation
-
additional information
-
all tumors with complete 1p19q codeletion are mutated in the IDH1 or IDH2 gene. Glioma patients having IDH1/IDH2 mutations show inproved median overall survival, different outcomes in WHO grade II and III gliomas according to the 1p19q and IDH1/IDH2 statusses, overview
additional information
-
enzyme mutation R132H is involved in myelodysplastic syndrome
additional information
-
heterozygous mutations in the gene encoding IDH1 occur in certain human brain tumors, IDH is a strong factor in the development of gliomas. Tumor-derived IDH1 mutations impair the enzyme's affinity for its substrate and dominantly inhibit wild-type IDH1 activity through the formation of catalytically inactive heterodimers. HIF-1alpha levels are higher in human gliomas harboring an IDH1 mutation than in tumors without a mutation. Rise in HIF-1alpha levels occur, reversible by an 2-oxoglutarate derivative
additional information
-
knockdown of IDPc expression in HEK293 cells greatly enhances apoptosis induced by cadmium. DNA fragmentation is enhanced in IDPc siRNA-transfected HEK293 cells compared to control cells upon exposure to cadmium
additional information
mutations in the enzyme cytosolic IDH1 at R132 are a common feature of a major subset of primary human brain cancers, especially in grade II-III gliomas and secondary glioblastomas. The mutations result in loss of the enzyme's ability to catalyze conversion of isocitrate to 2-oxoglutarate. Expression of R132H mutant IDH1 results in no measurable production of NADPH from isocitrate, and isocitrate-dependent NADPH production increases with increasing amounts of wild-type enzyme
additional information
-
mutations in the enzyme cytosolic IDH1 at R132 are a common feature of a major subset of primary human brain cancers, especially in grade II-III gliomas and secondary glioblastomas. The mutations result in loss of the enzyme's ability to catalyze conversion of isocitrate to 2-oxoglutarate. Expression of R132H mutant IDH1 results in no measurable production of NADPH from isocitrate, and isocitrate-dependent NADPH production increases with increasing amounts of wild-type enzyme
additional information
-
siRNA-mediated knockdown of IDPm suppresses hypoxia-induced stimulation of HIF-1alpha protein expression in PC-3 human prostate cancer cells
additional information
-
molecular enzyme structure and active site modelling, QM/MM calculations, and structure-function analysis, detailed overview
additional information
three-dimensional structure modelling, isocitrate substrate docking, overview
additional information
-
three-dimensional structure modelling, isocitrate substrate docking, overview
additional information
three-dimensional structure modelling, isocitrate substrate docking, overview
additional information
-
three-dimensional structure modelling, isocitrate substrate docking, overview
additional information
-
three-dimensional structure modelling, isocitrate substrate docking, overview
-
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
105000
40000
45000
45400
45800
45837
Q8X277
x * 45837, sequence calculation, x * 60000, recombinant, renatured enzyme, SDS-PAGE
46000
46381
-
x * 46381, isozyme IDP1, mass spectrometry, x * 46562, isozyme IDP2, mass spectrometry, x * 47856, isozyme IDP3, mass spectrometry
46562
-
x * 46381, isozyme IDP1, mass spectrometry, x * 46562, isozyme IDP2, mass spectrometry, x * 47856, isozyme IDP3, mass spectrometry
46600
-
2 * 46600, recombinant thrombin cleaved wild-type and mutant enzymes, SDS-PAGE
47000
47856
-
x * 46381, isozyme IDP1, mass spectrometry, x * 46562, isozyme IDP2, mass spectrometry, x * 47856, isozyme IDP3, mass spectrometry
48000
49000
52600
53000
55000
60000
68000
70000
75000 - 80000
80000
83000
recombinant His6-tagged enzyme, gel filtration
85000
86000
87000
90000
45000
x * 45000, recombinant N-terminally His6-tagged enzyme, SDS-PAGE
45400
2 * 45400, equilibrium of dimeric and tetrameric species, calculated from sequence
45400
4 * 45400, equilibrium of dimeric and tetrameric species, calculated from sequence
47000
x * 47000, approximately, cytosolic and mitochondrial isozymes, SDS-PAGE
49000
-
2 * 49000, isoform ICD-1, 2 * 86000, isoform ICD-2, SDS-PAGE. Besides dimers, isoform ICD-1 forms some tetramer, ICD-2 forms trimer
49000
-
4 * 49000, isoform ICD-1, SDS-PAGE. Main form is dimer for isoform ICD-1
60000
Q8X277
x * 45837, sequence calculation, x * 60000, recombinant, renatured enzyme, SDS-PAGE
86000
-
2 * 49000, isoform ICD-1, 2 * 86000, isoform ICD-2, SDS-PAGE. Besides dimers, isoform ICD-1 forms some tetramer, ICD-2 forms trimer
86000
-
and dimer, 3 * 86000, SDS-PAGE and chemical crosslinking, isoform ICD-2
90000
-
recombinant maltose binding fusion proteins, wild-type and mutant enzymes, gel filtration
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
homodimer
monomer
tetramer
trimer
-
and dimer, 3 * 86000, SDS-PAGE and chemical crosslinking, isoform ICD-2
additional information
?
Q8X277
x * 45837, sequence calculation, x * 60000, recombinant, renatured enzyme, SDS-PAGE
?
x * 47000, approximately, cytosolic and mitochondrial isozymes, SDS-PAGE
?
-
x * 46381, isozyme IDP1, mass spectrometry, x * 46562, isozyme IDP2, mass spectrometry, x * 47856, isozyme IDP3, mass spectrometry
?
x * 45000, recombinant N-terminally His6-tagged enzyme, SDS-PAGE
dimer
Q8X277
the enzyme is a dimer at high salt concentration. Deactivation due to incubation of the enzyme at low NaCl concentrations is related to irreversible dissociation of the active dimeric species towards a monomer
dimer
-
2 * 49000, isoform ICD-1, 2 * 86000, isoform ICD-2, SDS-PAGE. Besides dimers, isoform ICD-1 forms some tetramer, ICD-2 forms trimer
dimer
-
2 * 46600, recombinant thrombin cleaved wild-type and mutant enzymes, SDS-PAGE
dimer
-
residues Arg314, Tyr316, Lys321, and Arg323 are not involved in subunit interaction
dimer
and tetramer, crystallization data and analytical ultracentrifugation
dimer
2 * 45400, equilibrium of dimeric and tetrameric species, calculated from sequence
dimer
-
2 * 45400, equilibrium of dimeric and tetrameric species, calculated from sequence
-
homodimer
2 * 48300, His-tagged enzyme, calculated from amino acid sequence
homodimer
2 * 45000, recombinant His6-tagged enzyme, SDS-PAGE
homodimer
-
2 * 45000, recombinant His6-tagged enzyme, SDS-PAGE
-
homodimer
each subunit has a Rossmann fold, and a common top domain of interlocking beta sheets
homodimer
-
each subunit has a Rossmann fold, and a common top domain of interlocking beta sheets
-
monomer
1 * 81000, calculated from amino acid sequence
tetramer
-
4 * 49000, isoform ICD-1, SDS-PAGE. Main form is dimer for isoform ICD-1
tetramer
and dimer, crystallization data and analytical ultracentrifugation
tetramer
4 * 45400, equilibrium of dimeric and tetrameric species, calculated from sequence
tetramer
-
4 * 45400, equilibrium of dimeric and tetrameric species, calculated from sequence
-
additional information
prediction and analysis of structures and conserved domains of pepper NADP-ICDH containing 172 alpha helices, 84 extended strands, 32 beta turn, and 127 random coils, homology modeling, overview
additional information
-
prediction and analysis of structures and conserved domains of pepper NADP-ICDH containing 172 alpha helices, 84 extended strands, 32 beta turn, and 127 random coils, homology modeling, overview
-
additional information
exchange of Arg132 to His affects the conformation equilibrium and the reorganization of the active-site. Also, not only the expected loss of key salt-bridge interactions between the guanidinium of R132 and the alpha/beta carboxylates of isocitrate, as well as changes in the network that coordinates the metal ion, but also an unexpected reorganization of the active-site, structure analyis, overview
additional information
-
exchange of Arg132 to His affects the conformation equilibrium and the reorganization of the active-site. Also, not only the expected loss of key salt-bridge interactions between the guanidinium of R132 and the alpha/beta carboxylates of isocitrate, as well as changes in the network that coordinates the metal ion, but also an unexpected reorganization of the active-site, structure analyis, overview
additional information
three-dimensional structure modelling, structure comparison with the enzyme from Staphylococcus aureus, overview
additional information
-
three-dimensional structure modelling, structure comparison with the enzyme from Staphylococcus aureus, overview
additional information
three-dimensional structure of Mtb ICDH-1, overview
additional information
-
three-dimensional structure of Mtb ICDH-1, overview
additional information
-
three-dimensional structure of Mtb ICDH-1, overview
-
additional information
three-dimensional structure modelling, structure comparison with the human enzyme, PDB IDs 1T09 and 1T0L, overview
additional information
-
three-dimensional structure modelling, structure comparison with the human enzyme, PDB IDs 1T09 and 1T0L, overview
additional information
-
three-dimensional structure modelling, structure comparison with the human enzyme, PDB IDs 1T09 and 1T0L, overview
-
additional information
the overall fold of the enzyme protein is resolved into large domain, small domain and a clasp domain. The monomeric structure reveals also a unique terminal domain involved in dimerization. The overall TtIDH structure exhibits a closed conformation with the conserved catalytic triad residues Tyr144, Asp248, and Lys191. Oligomerization of the protein is determined using interface area and subunitsubunit interactions between protomers
additional information
-
the overall fold of the enzyme protein is resolved into large domain, small domain and a clasp domain. The monomeric structure reveals also a unique terminal domain involved in dimerization. The overall TtIDH structure exhibits a closed conformation with the conserved catalytic triad residues Tyr144, Asp248, and Lys191. Oligomerization of the protein is determined using interface area and subunitsubunit interactions between protomers
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glutathionylation
nitration
the enzyme protein is a target of inhibitory nitric oxide-mediated posttranslational modification (nitration)
phosphoprotein
S-nitrosylation
glutathionylation
S-glutathionylation of Cys363 is involved in the inhibition of the cytosolic enzyme activity upon nitrosoglutathione treatments
glutathionylation
-
Cys269 of IDPc is a target for S-glutathionylation, this modification is reversed by dithiothreitol as well as enzymatically by cytosolic glutaredoxin in the presence of glutathione. Glutathionylated IDPc is significantly less susceptible than native protein to peptide fragmentation by reactive oxygen species and proteolytic digestion. Glutathionylation may play a protective role in the degradation of protein through the structural alterations of IDPc.
phosphoprotein
the enzyme is phosphorylated at Ser113 by Escherichia coli isocitrate dehydrogenase kinase/phosphatase
phosphoprotein
tyrosine phosphorylated enzyme shows a significantly lowered enzymatic activity
S-nitrosylation
the enzyme protein is a target of inhibitory H2S-mediated posttranslational modification (S-nitrosylation)
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystal structures of a native enzyme at 2.2 A, a pseudo-native enzyme at 2.1 A, and of the enzyme in complex with NADP+, Ca2+ and D-isocitrate at 2.3 A
hanging drop vapour diffusion technique with reservoir solution consisting of 0.6 M ZnSO4 and 0.1 M Na cacodylate, pH 6.3
hanging drop vapour diffusion method, 0.001 ml of 10 mg/ml protein in 12.5 mM 2-morpholinoethanesulfonic acid, pH 6.2, with 1.25 mM MnSO4, 1.25 mM dithiothreitol and 10% glycerol, is mixed with 0.001 ml of reservoir solution containing 25% w/v PEG 2000 MME, 0.2 M Tris-HCl, pH 7.3, and 0.2 M MgCl2, and with or without 0.001 ml of 10 mM NADP+, 3 days to 2 months, X-ray diffrcation structure determination and analysis at 1.8-1.9 A resolution, molecular replacement
substrate/cofactor-free structure in presence of Mg2+ shows a distinct open conformation and suggests the presence of low-energy conformers
-
crystals of native DpIDH are obtained by the sitting-drop, vapour-diffusion method. The crystals are grown at 8°C. Crystals of DpIDH in complex with isocitrate (DpIDH-iso) are obtained by the hanging drop method at 8 °C
hanging drop vapour diffusion method, purified recombinant His-tagged enzyme in complex with NADP+: equal volume of protein solution, containing 15 mg/ml enzyme, 20 mM Tris-HCl, pH 7.4, 100 mM NaCl, and 10 mM NADP+, and of reservoir solution, containing 100 mM MES, pH 6.5, 12% PEG 20000, at 4°C, purified recombinant His-tagged enzyme in complex with NADP+, isocitrate and Ca2+: equal volume of protein solution, containing 15 mg/ml enzyme, 20 mM Tris-HCl, pH 7.4, 100 mM NaCl, and 10 mM NADP+, 10 mM DL-isocitrate and 10 mM CaCl2, and of reservoir solution, containing 100 mM MES, pH 5.9, 20% PEG 6000, at 20°C, X-ray diffraction structure determination and analysis
-
hanging drop vapor diffusion method, using 0.1 M sodium citrate, pH 5.5, 16% (w/v) PEG 4000, 20% (v/v) isopropanol
wild type and mutant enzyme K256Q, sitting drop vapor diffusion method, using 0.1 M sodium citrate tribasic dehydrate (pH 5.6), 11.5% (v/v) 2-propanol and 10.8% (w/v) PEG 4000
purified ICDH-1 in complex with NADPH at Mn2+, hanging drop vapor diffusion method, 0.001 ml of protein in 5 mM NADPH, and 5 mM MnCl2 is mixed with 0.001 ml of reservoir solution containing 30% PEG 2000 and 0.1 M Tris-HCl, pH 8.0, room temperature, X-ray diffraction structure determination and analysis at 2.18 A resoltuion
crystal structures of Saccharomyces cerevesiae mitochondrial NADP-IDH Idp1p in binary complexes with coenzyme NADP+, or substrate isocitrate, or product 2-oxoglutarate, and in a quaternary complex with NADPH, 2-oxoglutarate, and Ca2+, which represent different enzymatic states during the catalytic reaction. Crystallization is carried out at 20°C using the hanging-drop vapor diffusion method
20 mg/ml purified recombinant wild-type and selenomethionine enzyme, complexed with Mn2+ and isocitrate, 4°C, hanging drop vapour diffusion method, for the wild-type enzyme: 0.002 ml of enzyme solution containing 0.1 M triethanolamine chloride, pH 7.7, 0.15 M Na2SO4, 8 mM DL-isocitrate, 4 mM MnSO4, plus equal volume of 20% PEG 6000, 3% glycerol, against 0.75 ml reservoir solution containing 0.1 M triethanolamine chloride, pH 7.7, 0.15 M Na2SO4, 8 mM DL-isocitrate, 4 mM MnSO4, and 40% w/v xylitol, for the selenomethionine enzyme: 0.002 ml of enzyme solution containing 0.1 M triethanolamine chloride, pH 7.7, 0.15 M Na2SO4, 8 mM DL-isocitrate, plus equal volume of 18% PEG 6000, 3% glycerol, against 0.75 ml reservoir solution containing 0.1 M triethanolamine chloride, pH 7.7, 0.15 M Na2SO4, and 18% PEG 6000, 7-10 days, X-ray diffraction structure determination and analysis at 2.7 A resolution, modeling
enzyme in ternary complex with citrate and cofactor NADP+, X-ray diffraction structure determination and analysis at 1.80 A resolution
sitting and hanging drop vapour diffusion method, using 100 mM cacodylate and 1.4 M sodium acetate, 10 mM citric acid , and 10 mM MnCl2, at pH 6.5-7.8 and 25°C
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
S113A
S113D
S113E
S113G
S113T
S113Y
R211M
C363S
the mutation does not perturb the enzymatic characteristics of the enzyme. However, the mutant is less affected by nitrosoglutathione treatment than the wild type enzyme
D253A/S257K/K260Q/R314D/H315I/T327A
site-directed mutagenesis, the mutant shows a witch in cofactor specificity from NADP+ to NAD+
D253A/S257K/K260Q/R314D/H315I/T327A
-
site-directed mutagenesis, the mutant shows a witch in cofactor specificity from NADP+ to NAD+
-
A325P/G326S
50% inactivation after 10 min at 91.3°C as compared to 87.5°C for wild-type enzyme
A336F
50% inactivation after 10 min at 74°C as compared to 87.5°C or wild-type enzyme
I321L
50% inactivation after 10 min at 88.9°C as compared to 87.5°C for wild-type enzyme
Y309I/I310L
50% inactivation after 10 min at 88.4°C as compared to 87.5°C for wild-type enzyme
Y309I/I310L/I321L/A325P/G326S
50% inactivation after 10 min at 90°C as compared to 87.5°C for wild-type enzyme
A741S
-
the mutant exhibits higher specific activity and thermostability than the wild type enzyme
E596L
-
the mutant exhibits higher specific activity and thermostability than the wild type enzyme
R153C
the mutation dramatically reduces the catalytic efficiency of the enzyme for isocitrate oxidation, which drops to 1.5% of the wild type enzyme. The mutant acquires a neomorphic ability of producing 2-hydroxyglutarate from 2-oxoglutarate
R153H
the mutation dramatically reduces the catalytic efficiency of the enzyme for isocitrate oxidation, which drops to 0.6% of the wild type enzyme. The mutant acquires a neomorphic ability of producing 2-hydroxyglutarate from 2-oxoglutarate
R291S/K343D/Y344I/V350A/Y390P
Q8X277
switch in coenzyme specificity from NADP+ to NAD+
A134D
the mutant shows severely reduced catalytic efficiency compared to the wild type enzyme
C269S
C379S
D273L
the mutant exhibits an about 170fold decrease in catalytic efficiency, driven by a 5.4fold decrease in kcat and 31fold increase in Km as compared to the wild type enzyme
D273N
the mutant has a more than 500fold decrease in kcat/Km, driven primarily through more than 300fold increase in Km as compared to the wild type enzyme
D273S
the mutant exhibits adecrease in catalytic efficiency, driven by a 2.5fold decrease in kcat and 200fold increase in Km as compared to the wild type enzyme
G123R
site-directed mutagenesis, mutation is located in the catalytic domain, the mutant shows reduced activity compared to the wild-type enzyme
H133Q
the mutant shows strongly reduced catalytic efficiency compared to the wild type enzyme
K217M
the mutant shows reduced catalytic efficiency as compared to the wild type enzym
K217Q
the mutant shows reduced catalytic efficiency as compared to the wild type enzym
K413Q
the acetylation surrogate mutant of isoform IDH2 exhibits lower oxidative reaction rates than wild type. 2-Hydroxyglutarate production by the mutant is largely diminished at the enzymatic and cellular level
R100Q
the mutant shows severely reduced catalytic efficiency compared to the wild type enzyme
R132A
the mutant shows severely reduced catalytic efficiency compared to the wild type enzyme
R132C
R132G
R132H
R132K
the mutant shows severely reduced catalytic efficiency compared to the wild type enzyme
R132L
R132N
the mutant shows severely reduced catalytic efficiency compared to the wild type enzyme
R132Q
the mutant shows severely reduced catalytic efficiency compared to the wild type enzyme
R132S
R132W
the mutant shows severely reduced catalytic efficiency compared to the wild type enzyme
R132X
R172K
IDH2 R172 mutation causes production and accumulation of 2-hydroxyglutarate in acute myelogenous leukemia cells
R172X
naturally occuring mutations of IDH2 in metastatic brain tumors
H590L/R601D
the mutant with strongly decreased activity wit NADP+ compared to the wild type enzyme displays a 0.183fold preference for NAD+ over NADP+
H590L/R601D/R650S
the mutant with severely decreased activity with NADP+ compared to the wild type enzyme displays a 5.93fold preference for NAD+ over NADP+
H590L/R601D
-
the mutant with strongly decreased activity wit NADP+ compared to the wild type enzyme displays a 0.183fold preference for NAD+ over NADP+
-
H590L/R601D/R650S
-
the mutant with severely decreased activity with NADP+ compared to the wild type enzyme displays a 5.93fold preference for NAD+ over NADP+
-
C245S
the activities of the mutant in the presence of Cd2+ are decreased as that of wild type enzyme
C379S
the activity of the mutant in the absence of Cd2+ is similar to that of the wild type enzyme, but the decrease of activity in the presence of Cd2+ is much reduced
L594E
-
the mutant is more thermolabile than wild type enzyme and has a lower specific activity at temperatures over 45°C
H309F
-
site-directed mutagenesis, inactive mutant, poor cofactor binding, altered secondary structure
H309Q
-
site-directed mutagenesis, inactive mutant, poor cofactor binding, altered secondary structure
H315Q
-
site-directed mutagenesis, 40fold increased Km for NADP+ compared to the wild-type enzyme
H319Q
-
site-directed mutagenesis, cofactor binding and kinetics similar to the wild-type enzyme, slightly reduced activity
K212Q
site-directed mutagenesis, highly decreased activity in both reaction directions compared to the wild-type enzyme, altered pH-dependency of the activity
K212R
site-directed mutagenesis, highly decreased activity in both reaction directions compared to the wild-type enzyme, altered pH-dependency of the activity
K212Y
site-directed mutagenesis, highly decreased activity in both reaction directions compared to the wild-type enzyme, altered pH-dependency of the activity
N97A
-
site-directed mutagenesis, decreased Vmax compared to the wild-type enzyme, slightly affected Km values, but increased pKa of the ionizable metal-liganded hydroxyl of enzyme-bound isocitrate compared to the wild-type enzyme
N97D
-
site-directed mutagenesis, highly decreased Vmax compared to the wild-type enzyme
R132X
-
mutation of an arginine residue in pig mitochondrial IDH2 equivalent to R132 in human IDH1 causes a dramatic increase in Km for isocitrate by a factor of 165, with minimal effect on Vmax
R314Q
-
site-directed mutagenesis, 10fold increased Km for NADP+ compared to the wild-type enzyme
S95A
-
site-directed mutagenesis, decreased Vmax, and increased Km for isocitrate and Mn2+ compared to the wild-type enzyme
S95D
-
site-directed mutagenesis, highly decreased Vmax compared to the wild-type enzyme
T78A
-
site-directed mutagenesis, decreased Vmax, and increased Km for isocitrate and Mn2+ compared to the wild-type enzyme
Y140E
site-directed mutagenesis, highly decreased activity in both reaction directions compared to the wild-type enzyme, unaltered Km for isocitrate and NADP+
Y140F
site-directed mutagenesis, highly decreased activity in both reaction directions compared to the wild-type enzyme, unaltered Km for isocitrate and NADP+
Y140K
site-directed mutagenesis, highly decreased activity in both reaction directions compared to the wild-type enzyme, unaltered Km for isocitrate and NADP+
Y140T
site-directed mutagenesis, highly decreased activity in both reaction directions compared to the wild-type enzyme, unaltered Km for isocitrate and NADP+, highly increased activation by added exogenous acetic acid and phenol compared to the wild-type enzyme
Y316L
-
site-directed mutagenesis, 4fold increased Km for NADP+ compared to the wild-type enzyme
D389N
reduction in apparent melting temperature by 21.8°C compared to wild-type
F205M
reduction in apparent melting temperature by 3.5°C compared to wild-type
R186M
no change in apparent melting temperature compared to wild-type
H590L/R601L
-
the mutations greatly reduce the affinity for NADP+, but fail to improve the ability to use NAD+ so the mutant has similar affinities to NADP+ and NAD+
K589T/H590L/R601L
-
the mutations greatly reduce the affinity for NADP+, but fail to improve the ability to use NAD+ so the mutant has similar affinities to NADP+ and NAD+
R322D
site-directed mutagenesis, the mutant shows an 41fold higher Km for NADP+ than the wild-type enzyme, and it shows NAD+-dependent activity in contrast to the wild-type enzyme
R322D
-
site-directed mutagenesis, the mutant shows an 41fold higher Km for NADP+ than the wild-type enzyme, and it shows NAD+-dependent activity in contrast to the wild-type enzyme
-
additional information
S113A
mutant enzyme with remarkably reduced enzymatic activity
S113D
the phosphorylation-mimicking mutant lacks almost all enzymatic activity
S113E
the phosphorylation-mimicking mutant lacks almost all enzymatic activity
S113G
mutant enzyme with remarkably reduced enzymatic activity
S113T
mutant enzyme with remarkably reduced enzymatic activity
S113Y
mutant enzyme with remarkably reduced enzymatic activity
R211M
disruption of the seven-membered inter-domain ionic network. In wild-type enzyme the unfolding and folding transitions occurrs at slightly different denaturant concentrations even after prolonged equilibration time. The difference between the folding and the unfolding profiles is decreased in the mutant R211M
R211M
-
disruption of the seven-membered inter-domain ionic network. In wild-type enzyme the unfolding and folding transitions occurrs at slightly different denaturant concentrations even after prolonged equilibration time. The difference between the folding and the unfolding profiles is decreased in the mutant R211M
-
C269S
-
activity of the C269S mutant is not affected by glutathione disulfide and no glutathionylated IDPc is observed with 5 mM glutathione disulfide confirming that Cys269 is a target of IDPc glutathionylation
C269S
-
site-directed mutagenesis, is not sensitive to inhibition by Cd2+ in contrast to the wild-type enzyme
C379S
-
glutathionylation of the C379S mutant is similar to that of wild type enzyme
C379S
-
site-directed mutagenesis, is inhibited by Cd2+ in a similar manner to the wild-type
R132C
IDH1 R132 mutations cause production and accumulation of 2-hydroxyglutarate in acute myelogenous leukemia cells. The mutation reduces the affinity for isocitrate, and increases the affinity for NADPH and 2-oxoglutarate, preventing the oxidative decarboxylation of isocitrate to 2-oxoglutarate, and facilitating the conversion of 2-oxoglutarate to 2-hydroxyglutarate
R132C
-
naturally occuring mutation C394T, genotyping in glioma samples, overview
R132C
naturally occuring mutation of IDH1 in melanoma metastasis of the lung
R132C
-
naturally occuring mutation of IDH1, results in 60fold increased Km for isocitrate compared to the wild-type IDH1
R132C
the mutant shows severely reduced catalytic efficiency compared to the wild type enzyme
R132G
IDH1 R132 mutations cause production and accumulation of 2-hydroxyglutarate in acute myelogenous leukemia cells
R132G
-
naturally occuring mutation C394G, genotyping in glioma samples, overview
R132G
the mutant shows severely reduced catalytic efficiency compared to the wild type enzyme
R132H
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
R132H
IDH1 R132 mutations cause production and accumulation of 2-hydroxyglutarate in acute myelogenous leukemia cells
R132H
naturally occuring mutant of IDH1, the mutation causes loss in binding affinity for both isocitrate and MgCl2 along with a 1000fold decrease in catalytic turnover. The mutant IDH1 directly converts 2-oxoglutarate to 2-hydroxyglutarate, that rapidly accumulates in the medium of cells expressing R132H mutant IDH1, metabolite profiling in comparison to the wild-type IDH1, overview. Mutation to histidine results in a significant shift in position of the highly conserved residues Y139 from the A subunit and K212' from the B subunit both of which are thought to be critical for catalysis by this enzyme family. exchange of Arg132 to His affects the conformation equilibrium and the reorganization of the active-site. Also, not only the expected loss of key salt-bridge interactions between the guanidinium of R132 and the alpha/beta carboxylates of isocitrate, as well as changes in the network that coordinates the metal ion, but also an unexpected reorganization of the active-site, structure analyis, overview
R132H
-
naturally occuring mutation G395A, genotyping in glioma samples, overview
R132H
-
naturally occuring mutation in myelodysplastic syndrome preceding acute myeloid leukemia. R132H alteration can be detected by immunohistochemistry using R132H mutation-specific antibodies, overview
R132H
-
naturally occuring mutation of IDH1, results in 94fold increased Km for isocitrate compared to the wild-type IDH1
R132H
the mutant shows severely reduced catalytic efficiency compared to the wild type enzyme
R132H
the mutant catalyzes the conversion of 2-oxoglutarate plus NADPH to D-2-hydroxyglutarate
R132L
-
naturally occuring mutation G395T, genotyping in glioma samples, overview
R132S
-
naturally occuring mutation C394A, genotyping in glioma samples, overview
R132S
-
naturally occuring mutation of IDH1, results in 70fold increased Km for isocitrate compared to the wild-type IDH1
R132X
-
identification of frequent IDH1 mutations in grade II and IV diffuse gliomas reducing the produciton of NADPH. Forced expression of mutant IDH1 in cultured cells reduces formation of the enzyme product, 2-oxoglutarate, and increases the levels of hypoxia-inducible factor subunit HIF-1alpha, a transcription factor that facilitates tumor growth when oxygen is low and whose stability is regulated by 2-oxoglutarate. IDH1 normally functions as a homodimer, we hypothesized that the mutant IDH1 molecules in tumor cells form heterodimers with wild-type molecules and, in so doing, dominantly inhibit the activity of wild-type IDH1
R132X
naturally occuring mutation of IDH1 in metastatic brain tumors
additional information
-
introduction of an icdh mutation into the cat2 background, in which increased availability of H2O2 causes perturbed redox homeostasis and induction of stress-related genes. Accumulation of oxidized glutathione and pathogen-related responses are enhanced in double cat2 icdh mutants compared to cat2. Single icdh mutants present constitutive induction of PR genes, enhanced resistance to bacteria in icdh, cat2 and cat2 icdh is quantitatively correlated with PR gene expression. However, the effect of icdh in both Col0 and cat2 backgrounds is not associated with enhanced accumulation of salicylic acid, phenotypes, overview
additional information
identification of naturally occurring peroxisomal NADP-ICDH (picdh) Arabidopsis mutant lines, designated as picdh-1 (SALK_072422) and picdh-2 (SALK_039193C) carrying a T-DNA insertion in exons 9 and in the 5'UTR, respectively. The mutation results in a lack of the peroxisomal NADP-ICDH in both picdh-1 and picdh-2 plants. There are no significant differences in phenotype between the wild-type (Wt) and the two mutant (picdh-1 and picdh-2) lines. Intrinsic photosynthetic performance is not altered in the different plants with similar maximum C assimilation capacities, light use efficiency, and respiration rates in darkness due to similar growth rates. No differences are found in growth rates, stomatal densities, or leaf mass-area ratios
additional information
-
identification of naturally occurring peroxisomal NADP-ICDH (picdh) Arabidopsis mutant lines, designated as picdh-1 (SALK_072422) and picdh-2 (SALK_039193C) carrying a T-DNA insertion in exons 9 and in the 5'UTR, respectively. The mutation results in a lack of the peroxisomal NADP-ICDH in both picdh-1 and picdh-2 plants. There are no significant differences in phenotype between the wild-type (Wt) and the two mutant (picdh-1 and picdh-2) lines. Intrinsic photosynthetic performance is not altered in the different plants with similar maximum C assimilation capacities, light use efficiency, and respiration rates in darkness due to similar growth rates. No differences are found in growth rates, stomatal densities, or leaf mass-area ratios
-
additional information
-
introduction of an icdh mutation into the cat2 background, in which increased availability of H2O2 causes perturbed redox homeostasis and induction of stress-related genes. Accumulation of oxidized glutathione and pathogen-related responses are enhanced in double cat2 icdh mutants compared to cat2. Single icdh mutants present constitutive induction of PR genes, enhanced resistance to bacteria in icdh, cat2 and cat2 icdh is quantitatively correlated with PR gene expression. However, the effect of icdh in both Col0 and cat2 backgrounds is not associated with enhanced accumulation of salicylic acid, phenotypes, overview
-
additional information
-
construction of an NADP+-ICDH gene (icdA)-overexpressing strain (OPI-1) using Aspergillus niger strain WU-2223L. The amount of citric acid produced by Aspergillus niger can be altered with the NADP+-ICDH activity. Time-dependent transcriptional changes in the genes encoding NADP+-ICDH, NAD+-ICDH, and ICL are analyzed by RT-PCR. The glyoxylate cycle is poorly activated or slightly repressed in the icdA-overexpressing Aspergillus niger clone
additional information
the coenzyme specificity of BlIDH can be completely reversed from NADP+ to NAD+ by a factor of 2387 by replacing six residues. The loss in NADP+-dependent activity might result from the removal of favorable interactions between Arg314 or His315 and the 2'-phosphate group
additional information
-
the coenzyme specificity of BlIDH can be completely reversed from NADP+ to NAD+ by a factor of 2387 by replacing six residues. The loss in NADP+-dependent activity might result from the removal of favorable interactions between Arg314 or His315 and the 2'-phosphate group
-
additional information
-
analysis of IDH1 mutations in chromosome 19, 1p19q, and prognostic impact in glioma patients, overview
additional information
-
mutational analysis of IDH1 codon 132 in 1185 cancer samples, overview
additional information
-
siRNA-mediated knockdown of IDPm suppresses hypoxia-induced stimulation of HIF-1alpha protein expression in PC-3 human prostate cancer cells. Treatment with the 26S proteasome inhibitor MG132 fails to abrogate the suppression of HIF-1alpha accumulation induced by IDPm knockdown, whereas HIF-1alpha levels are reduced by cycloheximide treatment in both control and IDPm siRNA-transfected cells
additional information
-
transfection of HEK-293 cells with an IDPc small interfering RNA significantly decreases the activity of IDPc and enhances cellular susceptibility to cadmium-induced apoptosis as indicated by the morphological evidence of apoptosis, DNA fragmentation and condensation, cellular redox status, mitochondria redox status and function, and the modulation of apoptotic marker proteins, overview. DNA fragmentation is enhanced in IDPc siRNA-transfected HEK293 cells compared to control cells upon exposure to cadmium
additional information
-
two independent short hairpin RNAs decrease IDH1 mRNA by more than 75% and reduce cellular 2-oxoglutarate levels by up to 50%
additional information
-
construction of transgenic mice by infection of fertilized eggs, enzyme overexpressing transgenic mice show increased triglyceride and cholesterol levels and develop fatty liver, hyperlipidemia, and obesity
additional information
Idh2 gene deletion, generation of Idh2-/- mice, phenotype,overview
additional information
-
Idh2 gene deletion, generation of Idh2-/- mice, phenotype,overview
-
additional information
knockdown of IDPm by siRNA in H9c2 cells, the suppression of IDPm expression by siRNA induces apoptosis and hypertrophy of cultured cardiomyocytes through the disruption of cellular redox balance, phenotype, overview
additional information
-
construction of IDP1, IDP2, and IDP3 disruption mutants, and of double and triple disruption mutants in haploid strain MMY011. Complementation study in disruption mutants expressing the full-length IDPA enzyme from Aspergillus nidulans, which behaves similar to the yeast IDP2 harboring a type I peroxisomal targeting sequence, PTS1, and occurs in cytosol and peroxisomes, subcellular localization study, overview. Expression of IDPA lacking the mitochondrial targeting sequence and containing a different PTS1 results in the same expression level and subcellular orientation
additional information
-
construction of IDP1, IDP2, and IDP3 disruption mutants, and of double and triple disruption mutants in haploid strain MMY011. Complementation study in disruption mutants expressing the full-length IDPA enzyme from Aspergillus nidulans, which behaves similar to the yeast IDP2 harboring a type I peroxisomal targeting sequence, PTS1, and occurs in cytosol and peroxisomes, subcellular localization study, overview. Expression of IDPA lacking the mitochondrial targeting sequence and containing a different PTS1 results in the same expression level and subcellular orientation
-
additional information
engineering the 2-oxoglutarate overproduction from raw glycerol by overexpression of the genes encoding NADP+-dependent isocitrate dehydrogenase and pyruvate carboxylase in Yarrowia lipolytica. Overexpression of NADP+-dependent isocitrate dehydrogenase IDP1 or simultaneous overexpression of IDP1 and pyruvate carboxylase gene PYC1 strongly increase the amount of secreted 2-oxoglutarate
additional information
-
engineering the 2-oxoglutarate overproduction from raw glycerol by overexpression of the genes encoding NADP+-dependent isocitrate dehydrogenase and pyruvate carboxylase in Yarrowia lipolytica. Overexpression of NADP+-dependent isocitrate dehydrogenase IDP1 or simultaneous overexpression of IDP1 and pyruvate carboxylase gene PYC1 strongly increase the amount of secreted 2-oxoglutarate
additional information
-
engineering the 2-oxoglutarate overproduction from raw glycerol by overexpression of the genes encoding NADP+-dependent isocitrate dehydrogenase and pyruvate carboxylase in Yarrowia lipolytica. Overexpression of NADP+-dependent isocitrate dehydrogenase IDP1 or simultaneous overexpression of IDP1 and pyruvate carboxylase gene PYC1 strongly increase the amount of secreted 2-oxoglutarate
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
10 - 15
30
30 - 50
-
after incubation at 25°C and 30°C, the enzyme activity loses 31% and 69% of ist activity, respectively, and no activity is detected after incubation at 50°C
35 - 39
the enzyme is stable below 35°C. The enzyme sustains 50% activity after incubation at 39°C for 20 min with Mn2+ and 38°C with Mg2+
35 - 42
-
the enzyme is stable below 35°C, but its activity decreases rapidly above 35°C. The enzyme is almost inactivated after incubation at 42.5°C for 20 min
38 - 50
about 50% of IDH activity is preserved at 38°C after 20 min of incubation, the enzyme is inactive at 50°C
40
40 - 70
-
after incubation at temperatures up to 40°C, the wild type enzyme maintains its activity, but its residual activity is decreased by incubation at over 45°C and is lost after incubation at 70°C
45
45 - 55
purified recombinant enzyme, stable up to 45°C, enzyme activity drops quickly above this temperature, incubation at 50°C for 20 min causes a 40% loss of activity, while incubation at 55°C almost inactivates the enzyme
50
50 - 75
the enzyme retains full activity at 50°C and loses ca. 50% of its activity after 1 h of incubation at 75°C
54
60
65
70
80
88
additional information
10 - 15
stable at, purified recombinant His-tagged isozyme IDH-IIa
10 - 15
stable at, purified recombinant His-tagged isozyme IDH-IIb
30
-
the enzyme loses 74% of the activity after incubation for 10 min at 30°C
40
inactivation, purified recombinant His-tagged isozyme IDH-IIa
40
inactivation, purified recombinant His-tagged isozyme IDH-IIb
40
stable up to, purified recombinant His-tagged isozyme IDH-I
40
purified recombinant enzyme, 20 min, loss of 50% of enzyme activity, with Mg2+
45
enzyme BlIDH retains 50% of maximal activity after incubation at 45°C for 20 min with either Mn2+ or Mg2+
45
purified recombinant enzyme, 20 min, loss of 50% of enzyme activity, with Mn2+
50
inactivation, purified recombinant His-tagged isozyme IDH-I
60
Q8X277
recombinant enzyme, 93% remaining activity after 117 h, in presence of 3 M NaCl
65
-
30 min, isoform ICD-1, irreversible thermal inactivation, isoform ICD-2, renaturation of inactivated protein by slow cooling till 55°C
80
Q8X277
recombinant enzyme, inactivation within 2.5 min, in presence of 3 M NaCl
88
10 min, 50% loss of activity, wild-type enzyme and mutant enzyme Y309I/I310L
additional information
thermal denaturation is an irreversible process
additional information
thermal stability of wild-type and chimeric enzymes
additional information
-
thermal stability of wild-type and chimeric enzymes
additional information
thermal stability of wild-type and chimeric enzymes
additional information
-
thermal stability of wild-type and chimeric enzymes
additional information
-
the enzyme is incubated in Tris/EDTA/Mg2+ buffer containing either 0.5 M or 3 M KCl. The thermal stability of the enzyme is substantially reduced at the lower KCl concentration, with concomitant differences in the activation energies for the thermal inactivation process. Omission of Mg2+ from the incubation buffer greatly accelerates the rate of loss of activity, and its presence plus that of 3 M KCl are recommended for storage of the enzyme
additional information
thermal denaturation is an irreversible process
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
enzyme stability is mainly sensitive to cations and very little or not sensitive to anions. Divalent cations induce a strong shift of the active/inactive transition towards low salt concentration. Deactivation due to incubation of the enzyme at low NaCl concentrations is related to irreversible dissociation of the active dimeric species towards a monomer, which can be described as an extended inactive monomeric species
Q8X277
instable in solutions of low ionic strength, stabilization by ammonium sulfate
low molecular weight form of Acinetobacter calcoaceticus enzyme more heat stable than high molecular weight form
-
the activity of the enzyme treated with Escherichia coli isocitrate dehydrogenase kinase/phosphatase immediately decreases by 80% within 9 min
the enzyme activity drops continuously per time during 500 min measurements with an average lost of 1.1% of enzyme activity per 10 min
-
the inter-domain ionic network might be responsible for additional stabilization through a significant kinetic barrier in the unfolding pathway that can explain the larger difference observed between the folding and unfolding transitions of the wild type comparted to the mutant enzyme R211M
instable in solutions of low ionic strength, stabilization by ammonium sulfate
-
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OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
enzyme activity is affected by oxidative agents like oxidized glutathione and nitrosoglutathione through modifications of conserved Cys residues in the protein
760361
isozyme IDP3 shows highest defense against endogeneous oxidative stress
-
654367
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-18C, purified enzyme, 50% glycerol, stable for at least 1.5-2 months
-80°C, partially purified cytosolic and mitochondrial isozymes, several months, stable
-
-18C, purified enzyme, 50% glycerol, stable for at least 1.5-2 months
-
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
41fold by ultracentrifugation, ammonium sulfate fractionation, gel filtration and ion exchange chromatography, and desalting
-
by ultracentrifugation, ammonium sulfate fractionation, gel filtration and ion exchange chromatography, and desalting
-
glutathione-Sepharose column chromatography and DEAE-Sepharose chromatography
His-tagged enzyme is purified by TALON resin column chromatography, ICDH fused maltose-binding protein is purified by amylose resin chromatography
isozymes ICDH1, 172fold, and ICDH2, 31fold, by ammonium sulfate fractionation, desalting, DEAE ion exchange and gel filtration
-
NADP-isocitrate dehydrogenase from the normoxic and ischemic rat myocardium
native enzyme by PEG fractionation, affinity and hydrophobic interaction chromatography
-
Ni-NTA agarose column chromatography
Ni-NTA column chromatography
recombinant enzyme from Escherichia coli by ion exchange and gel filtration to homogeneity, 1.84fold
-
recombinant enzyme variants fused to the maltose binding fusion protein, from Escherichia coli, to homogeneity by amylose affinity, and ion exchange chromatography
recombinant His-tagged enzyme from Escherichia coli by nickel affinity chromatography
-
recombinant His-tagged enzyme from Escherichia coli strain DH5alpha by nickel affinity chromatography
recombinant His-tagged IDPA from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
-
recombinant His-tagged isozymes IDP1 and IDP2 by nickel affinity chromatography
-
recombinant His-tagged mutant enzymes C269S and C379S from Escherichia coli by nickel affinity chromatography
-
recombinant His-tagged wild-type and mutant IDH1s from Escherichia coli by nickel affinity chromatography
-
recombinant His6-tagged enzyme from Escherichia coli strain Rosetta (DE3)
-
recombinant His6-tagged enzyme from Escherichia coli strain Rosetta (DE3) by Co2+ affinity chromatography
recombinant His6-tagged enzyme from Escherichia coli strain Rosetta (DE3) by metal affinity chromatography
recombinant His6-tagged wild-type and mutant enzymes from Escherichia coli strain Rosetta (DE3) b metal affinity chromatography
recombinant N-terminally His6-tagged enzyme by nickel affinity chromatography and gel filtration
recombinant N-terminally His6-tagged enzyme from Escherichia coli by nickel affinity chromatography
recombinant solubilized enzyme by ultrafiltration, and DEAE ion exchange chromatography, 6.4fold
Q8X277
recombinant wild-type and mutant enzymes from Escherichia coli, cleavage of the fusion proteins by thrombin, to homogeneity by amylose affinity chromatography
-
recombinant wild-type and mutant enzymes from Escherichia coli, to homogeneity
recombinant wild-type and mutant enzymes from Escherichia coli, to homogeneity by amylose affinity chromatography, thrombin digestion, and DEAE ion exchange chromatography
-
recombinant wild-type and mutant maltose binding fusion proteins from Escherichia coli by amylose affinity and size exclusion chromatography
-
TALON metal affinity resin column chromatography
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
2 polymorphic isozymes IDHP-A and IDHP-B, isozymes show allelic variants in populations belonging to different living heights in the stream, analysis of allelic frequencies, overview
-
construction of a genomic cDNA library, gene Cl-idh, DNA sequence determination and analysis, expression in Escherichia coli strain BL21(DE3)
-
DNA and amino acid sequence determination and analysis, expression as Strep-tagged protein in Escherichia coli BLR(DE3) exclusively in inclusion bodies, removal of 27 amino acids from the N-terminus results in expression of partially soluble protein
-
exchange of promotors and altering of organellar targeting for expression of isozymes IDO2 and IDO3 in mitochondria, and of isozymes IDP1 and IDP3 in the cytosol, functional complementation studies using mutant strains
-
expressed in enzyme-defective Escherichia coli strain DEK2004
expressed in Escherichia coli BL21(DE3) cells
expressed in Escherichia coli Rosetta (DE3) cells
expression in Escherichia coli
expression in Escherichia coli as maltose binding fusion protein, wild-type and selenomethionine enzyme variants
expression of His-tagged IDPA in Escherichia coli strain BL21(DE3), expression of IDPA inm Saccharomyces cerevisiae, it behaves similar to the yeast IDP2 harboring a type I peroxisomal targeting sequenceand occurs in cytosol and peroxisomes, complementation study in Saccharomyces cerevisiae disruption mutants expressing the full-length IDPA enzyme from Aspergillus nidulans, and IDPA lacking the mitochondrial targeting sequence and containing a different PTS1, which results in the same expression level and subcellular orientation, subcellular localization study, overview
-
expression of isozyme IDP1 and IDP2 as His-tagged enzymes in a disruption mutant
-
expression of mouse isoenzyme IDP2 in Escherichia coli or Saccharomyces cerevisiae. Mouse enzyme can compensate for loss of yeast cytosolic IDP2 and of peroxisomal IDP3IDP3. Removal of the peroxisomal targeting signal of the mouse enzyme precludes both localization in peroxisomes and compensation for loss of yeast IDP3
expression of myc-tagged wild-type IDH1 and R132H mutant IDH1 in U-87MG glioblastoma cells
expression of the cDNA in a construct of nucleotides 1-1714 with rat PEPCK promotor and the SV-40 polyadenylation signal, permanant expression in 3T3-L1 cells and in transgenic mice, the latter are constructed by infection of fertilized eggs
-
expression of the gene in Escherichia coli by connecting it with the T7 promoter
expression of the IDH1R132H mutant at a level similar to the endogenous protein in the cytoplasm of glioblastoma U-87MG cells causes a dose-dependent reduction of 2-oxoglutarate levels. Overexpression of the IDH1R132H mutant in U-87MG cells stimulates expression of HIF-1alpha target genes. Overexpression of wild-type IDH1 reduces HIF-1alpha protein levels in HeLa and U-87MG cells. Expression of FLAG-tagged wild-type and R132 mutants IDH1 in HEK-293T cells and of His-tagged enzymes in Escherichia coli
-
expression of wild-type and mutant enzymes in Escherichia coli as maltose binding fusion proteins
-
expression of wild-type and mutant enzymes in Escherichia coli as maltose-binding fusion proteins
-
expression of wild-type and mutant enzymes in Escherichia coli TB1 as maltose binding fusion proteins
-
gene icd, phylogenetic analysis, recombinant expression of His6-tagged enzyme in Escherichia coli strain Rosetta (DE3)
gene icd, sequence comparisons, expression of His6-tagged in Escherichia coli strain Rosetta (DE3)
gene icd, sequence comparisons, recombinant expression of His6-tagged enzyme in Escherichia coli strain Rosetta (DE3)
gene icd-D or icd-I, genetic organization of ICD isozymes, recombinant overexpression of His-tagged isozyme IDH-I in IDH-deficient Escherichia coli strain DEK2004
gene icd-M or icd-II, genetic organization of ICD isozymes, recombinant overexpression of His-tagged isozyme IDH-IIa in IDH-deficient Escherichia coli strain DEK2004
gene icd-M or icd-II, genetic organization of ICD isozymes, recombinant overexpression of His-tagged isozyme IDH-IIb in IDH-deficient Escherichia coli strain DEK2004
gene idh, DNA and amino acid sequence determination and analysis, phylogenetic analysis, recombinant expression of His-tagged enzyme in Escherichia coli strain DH5alpha
gene idh1, expression of Myc-tagged wild-type and Myc-tagged mutant enzymes in HEK-293T cells
gene IDP1, overexpression in Yarrowia lipolytica strain H355A, and coexpression with pyruvate carboxylase gene PYC1
gene NADP-ICDH, DNA and amino acid sequence determination and analysis, phylogenetic tree
gene of mitochondrial isozyme, DNA and amino acid sequence determination and analysis, subcellular RT-PCR analysis of brain cells
gene pICDH, DNA and amino acid sequence determination and analysis, phylogenetic analysis
gene Rv3339c, expression of N-terminally His6-tagged enzyme
gene Tc00.1047053506925.319 or IDH2, recombinant expression of the N-terminally His6-tagged enzyme in Escherichia coli
gene Tc00.1047053511575.60 or IDH1, recombinant expression of the N-terminally His6-tagged enzyme in Escherichia coli, co-expression with bacterial GroEL/GroES chaperones is required for IDH1 in order to achieve a soluble enzyme
gene ZmIDH2, DNA and amino acid sequence determination and analysis, sequence comparisons, semi-quantitative RT-PCR expression analysis
IDCH gene, DNA and amino acid sequence determination by combinated PCR and screening of genomic lambda EMBL3 library, and sequence analysis, overexpression in Escherichia coli BL21(DE3) as insoluble protein in inclusion bodies
Q8X277
idh2, DNA and amino acid sequence determination and anaysis, phylogenetic analysis, overexpression of His6-tagged wild-type and mutant enzymes in Escherichia coli strain Rosetta (DE3)
NADP+-ICDH contains two different translational ATG start sites, fusion of mitochondrial and chloroplastic targeting signals to YFP reporter, and transient expression in Nicotiana tabacum using Agrobacterium tumefaciens transfection method. The chloroplast-tageting signal constructs are localizes in the chloroplast, while the mitochondrial constructs are localized in either in mitochondria and chloroplasts, due to an 50 amino acid additional part that is added in expression in cultivars Xanthi and Petit Havana
SdIDH, sequence comparisons, expression of His6-tagged enzyme in Escherichia coli strain Rosetta (DE3)
-
wild-type and mutant enzymes are expressed in Escherichia coli
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
immediately following application of hypoosmotic stress, the activity of the enzyme in leaves decreases compared to plants grown in soil. After 3 days, a defense response appears in the form of substantially (3.1fold) increased specific activities in hypoosmotically stressed leaves
-
in root tissue, the enzyme expression is upregulated under both chronic as well as transient N-stress conditions
in shoot tissue, the enzyme expression is downregulated under chronic as well as in transient N-stress treatments
ischemia-reperfusion reduces IDH2 expression and activity in both Idh2+/+ and Idh2-/- kidneys. IDH1 expression decreases 1 day after ischemia and then returns to around normal level by 16 days after ischemia
plants exposed to salt stress for three days exhibit significantly (1.7fold) increased specific activity in leaves compared to non-stressed controls grown in soil
-
the enzyme is induced by drought and salt stress both in transcription and protein levels
transfection of HeLa cells with siRNA leading to decreased activity of IDPm and enhanced susceptibility of the cells to selenite-induced apoptosis, overview
-
ischemia-reperfusion reduces IDH2 expression and activity in both Idh2+/+ and Idh2-/- kidneys. IDH1 expression decreases 1 day after ischemia and then returns to around normal level by 16 days after ischemia
ischemia-reperfusion reduces IDH2 expression and activity in both Idh2+/+ and Idh2-/- kidneys. IDH1 expression decreases 1 day after ischemia and then returns to around normal level by 16 days after ischemia
-
-
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RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
isoform ICD-2, renaturation of protein inactivated for 30 min at 65°C by slow cooling till 55°C
-
overnight dialysis against guanidine-HCl, GDP buffer
oxidized glutathione leads to enzyme inactivation with simultaneous formation of a mixed disulfide between glutathione and the cysteine residues of enzyme. Enzymical reactivation by glutaredoxin2 in presence of reduced glutathione
-
solubilization in presence of 3 M NaCl of recombinant enzyme from inclusion bodies after expression in Escherichia coli
Q8X277
with 2-mercaptoethanol after inactivation at 40°C, isoenzyme II, 40% renaturation
-
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
biotechnology
-
the icdA gene is a potentially valuable tool for modulating citric acid production by metabolic engineering
diagnostics
medicine
additional information
analysis
-
simultaneous detection, quantitation and purification of glucose 6-phosphate dehydrogenase, malic enzyme, and NADP-dependent isocitrate dehydrogenase by blue native gel electrophoresis
analysis
-
simultaneous detection, quantitation and purification of glucose 6-phosphate dehydrogenase, malic enzyme, and NADP-dependent isocitrate dehydrogenase by blue native gel electrophoresis
-
diagnostics
-
IDH1 codon 132 mutation is an important prognostic biomarker in gliomas. IDH1 mutation predicts outcome in grade 2, 3, and 4 gliomas
diagnostics
-
IDH1 mutational analysis can serve as a useful diagnostic marker of a glioma
medicine
sensitizing effect of NADP+-dependent isocitrate dehydrogenase siRNA on the apoptotic cell death of HeLa cells offers the possibility of developing a modifier of cancer therapy
medicine
-
the sensitizing effect of NADP+-dependent isocitrate dehydrogenase siRNA on the apoptotic cell death of HeLa cells offers the possibility of developing a modifier of cancer chemotherapy
medicine
transfection of HeLa cells with an NADP+-dependent isocitrate dehydrogenase small interfering RNA decreased the activity of IDPm, enhancing the susceptibility of radiation-induced apoptosis. The effect of NADP+-dependent isocitrate dehydrogenaseIDPm small interfering RNA on HeLa cells offers the possibility of developing a modifier of radiation therapy
medicine
the sensitizing effect of IDPm siRNA and autophagy inhibitor on the ionizing radiation induced apoptotic cell death of glioma cells offers a novel redox-active therapeutic strategy for the treatment of cancer
medicine
the enzyme is a vaccine candidate against the fish pathogen Edwardsiella tarda infection. The serum of enzyme-vaccinated flounder exhibit the highest bactericidal activity compared with other groups. The recombinant enzyme can enhance the expressions of interferon-gamma, natural killer enhancing factor, interleukin-6, major histocompatibility complex Ialpha, CD4-1 and CD8alpha
medicine
-
the enzyme is a vaccine candidate against the fish pathogen Edwardsiella tarda infection. The serum of enzyme-vaccinated flounder exhibit the highest bactericidal activity compared with other groups. The recombinant enzyme can enhance the expressions of interferon-gamma, natural killer enhancing factor, interleukin-6, major histocompatibility complex Ialpha, CD4-1 and CD8alpha
-
additional information
-
IDPm siRNA functions as a potentially useful agent for targeting chemo- and radio-resistant hypoxic cells within solid tumors through inhibition of HIF-1alpha expression
additional information
-
future clinical and bioengineering applications of hICDH can be in the development of techniques to regulate the growth of glioblastomas and to capture and store carbon dioxide
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Release 2023.1 (January 2023)
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