Nature Structural Biology
8, 641 - 648 (2001)
doi:10.1038/89691
Structure of 4-diphosphocytidyl-2-C-
methylerythritol synthetase involved in mevalonate-
independent isoprenoid biosynthesisStéphane B. Richard1, Marianne E. Bowman1, Witek Kwiatkowski1, Ilgu Kang2, Cathy Chow2, Antonietta M. Lillo2, David E. Cane2
& Joseph P. Noel11
Structural Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA. 2
Department of Chemistry, Brown University, Providence, Rhode Island 02912, USA.
Correspondence should be addressed to Joseph P. Noel noel@sbl.salk.eduThe 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.
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