PMID:11427897

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Citation

Richard, SB, Bowman, ME, Kwiatkowski, W, Kang, I, Chow, C, Lillo, AM, Cane, DE and Noel, JP (2001) Structure of 4-diphosphocytidyl-2-C- methylerythritol synthetase involved in mevalonate- independent isoprenoid biosynthesis. Nat. Struct. Biol. 8:641-8

Abstract

The YgbP protein of Escherichia coli encodes the enzyme 4-diphosphocytidyl-2-C-methylerythritol (CDP-ME) synthetase, a member of the cytidyltransferase family of enzymes. CDP-ME is an intermediate in the mevalonate-independent pathway for isoprenoid biosynthesis in a number of prokaryotic organisms, algae, the plant plastids and the malaria parasite. Because vertebrates synthesize isoprenoid precursors using a mevalonate pathway, CDP-ME synthetase and other enzymes of the mevalonate-independent pathway for isoprenoid production represent attractive targets for the structure-based design of selective antibacterial, herbicidal and antimalarial drugs. The high-resolution structures of E. coli CDP-ME synthetase in the apo form and complexed with both CTP-Mg2+ and CDP-ME-Mg2+ reveal the stereochemical principles underlying both substrate and product recognition as well as catalysis in CDP-ME synthetase. Moreover, these complexes represent the first experimental structures for any cytidyltransferase with both substrates and products bound.

Links

PubMed Online version:10.1038/89691

Keywords

Apoenzymes/antagonists & inhibitors; Apoenzymes/chemistry; Apoenzymes/genetics; Apoenzymes/metabolism; Binding Sites; Catalysis; Crystallography, X-Ray; Cytidine Diphosphate/analogs & derivatives; Cytidine Diphosphate/chemistry; Cytidine Diphosphate/metabolism; Cytidine Triphosphate/chemistry; Cytidine Triphosphate/metabolism; Dimerization; Drug Design; Erythritol/analogs & derivatives; Erythritol/metabolism; Escherichia coli/enzymology; Escherichia coli/genetics; Mevalonic Acid/metabolism; Models, Molecular; Mutation/genetics; Nucleotidyltransferases/antagonists & inhibitors; Nucleotidyltransferases/chemistry; Nucleotidyltransferases/genetics; Nucleotidyltransferases/metabolism; Polyisoprenyl Phosphates/biosynthesis; Polyisoprenyl Phosphates/chemistry; Polyisoprenyl Phosphates/metabolism; Protein Structure, Secondary; Structure-Activity Relationship; Substrate Specificity; Sugar Phosphates/metabolism

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