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Literature summary 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

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

Protein Variants

EC Number Protein Variants Comment Organism
1.1.1.267 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

EC Number Inhibitors Comment Organism Structure
1.1.1.267 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
1.1.1.267 FR900098
-
 Plasmodium falciparum
1.1.1.267 additional information design and development of inhibitors, structure and docking modeling, overview Plasmodium falciparum

Metals/Ions

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

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.1.1.267 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+
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
1.1.1.267 Plasmodium falciparum O96693
-
-

Reaction

EC Number Reaction Comment Organism Reaction ID
1.1.1.267 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
a

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.1.1.267 1-deoxy-D-xylulose 5-phosphate + NADPH + H+
-
 Plasmodium falciparum 2-C-methyl-D-erythritol 4-phosphate + NADP+
-
 ?
1.1.1.267 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

EC Number Subunits Comment Organism
1.1.1.267 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

EC Number Synonyms Comment Organism
1.1.1.267 DXR
-
 Plasmodium falciparum

Cofactor

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