Literature summary for 1.1.1.37 extracted from

Roche, J.; Girard, E.; Mas, C.; Madern, D.
The archaeal LDH-like malate dehydrogenase from Ignicoccus islandicus displays dual substrate recognition, hidden allostery and a non-canonical tetrameric oligomeric organization (2019), J. Struct. Biol., 208, 7-17 .

Cloned(Commentary)

Cloned (Comment)	Organism
recombinant expression of His-tagged enzyme in Escherichia coli strain BL21(DE3)	Ignicoccus islandicus

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified recombinant His-tagged enzyme, sitting drop vapor diffusion method, mixing of 0.001 ml of 4 mg/ml protein in 50 mM Tris-HCl, pH 7.2, 50 mM NaCl, and 10 mM Tb-Xo4 crystallophore, with 0.001 ml of reservoir solution containing 10% PEG 6000 and 100 mM HEPES, pH 7.0, at 20°C, X-ray diffraction structure determination and analysis, molecular replacement using the structure of Haloferax volcanii MalDH (PDB ID 4BGU) as search template, modeling	Ignicoccus islandicus

Crystallization (Comment)

Organism

purified recombinant His-tagged enzyme, sitting drop vapor diffusion method, mixing of 0.001 ml of 4 mg/ml protein in 50 mM Tris-HCl, pH 7.2, 50 mM NaCl, and 10 mM Tb-Xo4 crystallophore, with 0.001 ml of reservoir solution containing 10% PEG 6000 and 100 mM HEPES, pH 7.0, at 20°C, X-ray diffraction structure determination and analysis, molecular replacement using the structure of Haloferax volcanii MalDH (PDB ID 4BGU) as search template, modeling

Ignicoccus islandicus

Inhibitors

Inhibitors	Comment	Organism	Structure
oxaloacetate	substrate inhibition	Ignicoccus islandicus

KM Value [mM]

KM Value [mM]	KM Value Maximum [mM]	Substrate	Comment	Organism	Structure
additional information	-	additional information	Michaelis-Menten and allosteric sigmoidal kinetics	Ignicoccus islandicus
0.38	-	oxaloacetate	pH 7.0, 70°C	Ignicoccus islandicus

Molecular Weight [Da]

Molecular Weight [Da]	Molecular Weight Maximum [Da]	Comment	Organism
124000	-	gel filtration	Ignicoccus islandicus
133000	-	about, sequence calculation	Ignicoccus islandicus

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.
oxaloacetate + NADH + H+	Ignicoccus islandicus	-	L-malate + NAD+	-	r
oxaloacetate + NADH + H+	Ignicoccus islandicus DSM 13165	-	L-malate + NAD+	-	r
pyruvate + NADH + H+	Ignicoccus islandicus	-	L-lactate + NAD+	-	r
pyruvate + NADH + H+	Ignicoccus islandicus DSM 13165	-	L-lactate + NAD+	-	r

Organism

Organism	UniProt	Comment	Textmining
Ignicoccus islandicus	A0A0U3FQH7	-	-
Ignicoccus islandicus DSM 13165	A0A0U3FQH7	-	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and gel filtration	Ignicoccus islandicus

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
additional information	Ignicoccus islandicus MalDH recognizes oxaloacetate as main substrate, but it is also able to use pyruvate	Ignicoccus islandicus	?	-	-
additional information	Ignicoccus islandicus MalDH recognizes oxaloacetate as main substrate, but it is also able to use pyruvate	Ignicoccus islandicus DSM 13165	?	-	-
oxaloacetate + NADH + H+	-	Ignicoccus islandicus	L-malate + NAD+	-	r
oxaloacetate + NADH + H+	best substrate	Ignicoccus islandicus	L-malate + NAD+	-	r
oxaloacetate + NADH + H+	-	Ignicoccus islandicus DSM 13165	L-malate + NAD+	-	r
oxaloacetate + NADH + H+	best substrate	Ignicoccus islandicus DSM 13165	L-malate + NAD+	-	r
pyruvate + NADH + H+	-	Ignicoccus islandicus	L-lactate + NAD+	-	r
pyruvate + NADH + H+	-	Ignicoccus islandicus DSM 13165	L-lactate + NAD+	-	r

Subunits

Subunits	Comment	Organism
More	the Ignicoccus islandicus MaDH amino-acid sequence predicts two domains: a NAD(P)-binding Rossmann-fold domain (residues 7 to 138) and a LDH C-terminal-like domain (residues 146 to 308), MalDH quaternary structure analysis and comparison, overview	Ignicoccus islandicus
tetramer	4 * 33500, about, sequence calculation	Ignicoccus islandicus

Synonyms

Synonyms	Comment	Organism
LDH-like malate dehydrogenase	-	Ignicoccus islandicus
NAD-dependent malate dehydrogenase	-	Ignicoccus islandicus
NAD-dependent MalDH	-	Ignicoccus islandicus

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
70	-	reduction of oxaloacetate	Ignicoccus islandicus

Turnover Number [1/s]

Turnover Number Minimum [1/s]	Turnover Number Maximum [1/s]	Substrate	Comment	Organism	Structure
8	-	pyruvate	pH 7.0, 70°C	Ignicoccus islandicus
444	-	oxaloacetate	pH 7.0, 70°C	Ignicoccus islandicus

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
7	-	reduction of oxaloacetate	Ignicoccus islandicus

Cofactor

Cofactor	Comment	Organism
additional information	no significant oxaloacetate (OAA) reduction is detected when NADPH was used as coenzyme at 70°C. the presence of an aspartic residue at position 54 of the alignment suggests that Ignicoccus islandicus MalDH would use NADH instead of NADPH, and the lack of NADPH recognition confirmes it. In contrast, those characterized as NADPH-dependent MalDHs have a glycine residue at this position. This is because the smaller size of glycine allows accommodating the additional phosphate of NADPH	Ignicoccus islandicus
NAD+	-	Ignicoccus islandicus
NADH	-	Ignicoccus islandicus

Ki Value [mM]

Ki Value [mM]	Ki Value maximum [mM]	Inhibitor	Comment	Organism	Structure
0.24	-	oxaloacetate	pH 7.0, 70°C	Ignicoccus islandicus

General Information

General Information	Comment	Organism
evolution	the enzyme belongs to the MalDH/LDH superfamily, which is divided into several phylogenetically related groups, lactate dehydrogenases (LDHs) and malate dehydrogenases (MalDHs) belong to a wide group of 2-oxoacid:NAD(P)-dependent dehydrogenases that catalyze the reversible conversion of 2-hydroxyacids to the corresponding 2-oxoacids, evolutionary history of the LDHs and MalDHs, overview. The enzyme structure belongs to the NAD(P)-binding Rossmann-like domain CATH superfamily	Ignicoccus islandicus
metabolism	when the competent catalytic state is reached, LDH catalyzes the direct transfer of a hydride ion from the pro-R face of NADH to the C2 carbon of pyruvate to produce lactate, whereas MalDH transforms oxaloacetate into malate	Ignicoccus islandicus
additional information	MalDH is an enzyme with intermediate properties between allosteric LDHs and non-allosteric tetrameric MalDHs. The catalytic residue is histidine H195. The structure of Ignicoccus islandicus MalDH resembles that of canonical LDHs. The amino acid at position 102 is considered as the most important substrate-discriminating residue between LDHs and MalDHs. Structure-function analysis and comparisons, overview	Ignicoccus islandicus

kcat/KM [mM/s]

kcat/KM Value [1/mMs^-1]	kcat/KM Value Maximum [1/mMs^-1]	Substrate	Comment	Organism	Structure
1168.4	-	oxaloacetate	pH 7.0, 70°C	Ignicoccus islandicus