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Literature summary for 1.1.1.267 extracted from

  • Singh, N.; Cheve, G.; Avery, M.A.; McCurdy, C.R.
    Comparative protein modeling of 1-deoxy-D-xylulose-5-phosphate reductoisomerase enzyme from Plasmodium falciparum: a potential target for antimalarial drug discovery (2006), J. Chem. Inf. Model., 46, 1360-1370.
    View publication on PubMed

Application

Application Comment Organism
drug development the enzyme is a potential target for antimalarial drug development and chemotherapy Plasmodium falciparum

Protein Variants

Protein Variants Comment Organism
H219Q site-directed mutagenesis, the mutation decreased the affinity toward the substrate 1-deoxy-D-xylulose 5-phosphate with an 8-fold increase in the Km compared to the wild-type enzyme Plasmodium falciparum

Inhibitors

Inhibitors Comment Organism Structure
fosmidomycin a natural antibiotic from Streptomyces lavendulae, a specific, mixed type inhibitor, the N-formyl-N-hydroxy amino headgroup of fosmidomycin coordinates Mg2+ ion forming an octahedral complex with active site residues Asp157, Glu159, and Glu241 and a critical binding site water molecule, residue His219 is essential for placing fosmidomycin in the active site for optimal catalysis, mechanism, overview, NADPH has a vital role in tight binding of the inhibitor within the enzyme active site Plasmodium falciparum
FR900098
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Plasmodium falciparum
additional information design and development of inhibitors, structure and docking modeling, overview Plasmodium falciparum

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ the enzyme requires divalent metal ions Plasmodium falciparum
Mn2+ the enzyme requires divalent metal ions Plasmodium falciparum

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1-deoxy-D-xylulose 5-phosphate + NADPH + H+ Plasmodium falciparum second step of the deoxyxylulose 5-phosphate/methylerythritol 4-phosphate pathway with end product isopentenylphosphate, overview 2-C-methyl-D-erythritol 4-phosphate + NADP+
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?

Organism

Organism UniProt Comment Textmining
Plasmodium falciparum O96693
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-

Reaction

Reaction Comment Organism Reaction ID
2-C-methyl-D-erythritol 4-phosphate + NADP+ = 1-deoxy-D-xylulose 5-phosphate + NADPH + H+ highly conserved active site structure, active site residues Asp157, Glu159, and Glu241, residue His219 is essential for placing the substrate in the active site for optimal catalysis Plasmodium falciparum

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
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Plasmodium falciparum 2-C-methyl-D-erythritol 4-phosphate + NADP+
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?
1-deoxy-D-xylulose 5-phosphate + NADPH + H+ second step of the deoxyxylulose 5-phosphate/methylerythritol 4-phosphate pathway with end product isopentenylphosphate, overview Plasmodium falciparum 2-C-methyl-D-erythritol 4-phosphate + NADP+
-
?

Subunits

Subunits Comment Organism
More detailed three-dimensional modeling and analysis of structure-function relationship, comparative modeling through multiple alignment followed by intensive optimization, minimization, and validation, the three-dimensional structure shows monomeric subunit consisting of three domains: an N-terminal NADPH binding domain, a connective or linker domain, with most of the active site residues located in this domain, and a C-terminal domain Plasmodium falciparum

Synonyms

Synonyms Comment Organism
DXR
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Plasmodium falciparum

Cofactor

Cofactor Comment Organism Structure
NADPH NADPH has a vital role in tight binding of the inhibitor fosmidomycin within the enzyme active site Plasmodium falciparum