1pcw
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(New page: 200px<br /><applet load="1pcw" size="450" color="white" frame="true" align="right" spinBox="true" caption="1pcw, resolution 1.85Å" /> '''Aquifex aeolicus KDO...)
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Revision as of 21:34, 20 November 2007
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Aquifex aeolicus KDO8PS in complex with cadmium and APP, a bisubstrate inhibitor
Overview
3-Deoxy-D-manno-octulosonate 8-phosphate (KDO8P) is the phosphorylated, precursor of KDO, an essential sugar of the lipopolysaccharide of Gram, negative bacteria. KDO8P is produced by a specific synthase (KDO8PS) by, condensing arabinose 5-phosphate (A5P) and phosphoenolpyruvate (PEP), with, release of inorganic phosphate. As KDO8PS is present in bacteria and, plants, but not in mammalian cells, and mutations that inactivate KDO8PS, also block cell replication, KDO8PS is a promising target for the design, of new antimicrobials that act by blocking lipopolysaccharide, biosynthesis. Previous studies have shown that a compound mimicking an, intermediate of the condensation reaction is a good ligand and a powerful, inhibitor. Here we report on the crystallographic investigation of the, binding to KDO8PS of new derivatives of this original inhibitor. The, structures of the enzyme in complex with these compounds, and also with, the PEP analogs, 2-phosphoglyceric acid (2-PGA) and Z-methyl-PEP, point to, future strategies for the design of novel inhibitors of KDO8PS.
About this Structure
1PCW is a Single protein structure of sequence from Aquifex aeolicus with CD and H4P as ligands. Active as 3-deoxy-8-phosphooctulonate synthase, with EC number 2.5.1.55 Full crystallographic information is available from OCA.
Reference
Structure-based design of novel inhibitors of 3-deoxy-D-manno-octulosonate 8-phosphate synthase., Xu X, Wang J, Grison C, Petek S, Coutrot P, Birck MR, Woodard RW, Gatti DL, Drug Des Discov. 2003;18(2-3):91-9. PMID:14675946
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