1PCW

Aquifex aeolicus KDO8PS in complex with cadmium and APP, a bisubstrate inhibitor

Summary for 1PCW

• Entry DOI: 10.2210/pdb1pcw/pdb
• Related: 1JCX
• Descriptor: 2-dehydro-3-deoxyphosphooctonate aldolase, CADMIUM ION, 1-DEOXY-6-O-PHOSPHONO-1-[(PHOSPHONOMETHYL)AMINO]-L-THREO-HEXITOL, ... (4 entities in total)
• Functional Keywords: beta(8)/alpha(8) barrel, lyase
• Biological source: Aquifex aeolicus
• Cellular location: Cytoplasm (By similarity): O66496
• Total number of polymer chains: 2
• Total formula weight: 60483.98

Authors

Xu, X.,Wang, J.,Grison, C.,Petek, S.,Coutrot, P.,Birck, M.,Woodard, R.W.,Gatti, D.L. (deposition date: 2003-05-17, release date: 2004-02-17, Last modification date: 2023-08-16)

Primary citation

Xu, X.,Wang, J.,Grison, C.,Petek, S.,Coutrot, P.,Birck, M.R.,Woodard, R.W.,Gatti, D.L.
Structure-Based Design of Novel Inhibitors of 3-Deoxy-D-manno-octulosonate 8-Phosphate Synthase.
Drug DES.DISCOVERY, 18:91-99, 2003

PubMed Abstract: 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.

PubMed: 14675946

Experimental method

X-RAY DIFFRACTION (1.85 Å)