2GKL

Crystal structure of the zinc carbapenemase CPHA in complex with the inhibitor pyridine-2,4-dicarboxylate

Summary for 2GKL

• Entry DOI: 10.2210/pdb2gkl/pdb
• Related: 1X8G 1X8H 1X8I
• Descriptor: Beta-lactamase, ZINC ION, PYRIDINE-2,4-DICARBOXYLIC ACID, ... (5 entities in total)
• Functional Keywords: hydrolase, lactamase, inhibitor, zn
• Biological source: Aeromonas hydrophila
• Cellular location: Periplasm (Probable): P26918
• Total number of polymer chains: 1
• Total formula weight: 25729.63

Authors

Garau, G.,Dideberg, O. (deposition date: 2006-04-03, release date: 2007-03-13, Last modification date: 2023-10-25)

Primary citation

Horsfall, L.E.,Garau, G.,Lienard, B.M.R.,Dideberg, O.,Schofield, C.J.,Frere, J.M.,Galleni, M.
Competitive Inhibitors of the CphA Metallo-{beta}-Lactamase from Aeromonas hydrophila
Antimicrob.Agents Chemother., 51:2136-2142, 2007

PubMed Abstract: Various inhibitors of metallo-beta-lactamases have been reported; however, none are effective for all subgroups. Those that have been found to inhibit the enzymes of subclass B2 (catalytically active with one zinc) either contain a thiol (and show less inhibition towards this subgroup than towards the dizinc members of B1 and B3) or are inactivators behaving as substrates for the dizinc family members. The present work reveals that certain pyridine carboxylates are competitive inhibitors of CphA, a subclass B2 enzyme. X-ray crystallographic analyses demonstrate that pyridine-2,4-dicarboxylic acid chelates the zinc ion in a bidentate manner within the active site. Salts of these compounds are already available and undergoing biomedical testing for various nonrelated purposes. Pyridine carboxylates appear to be useful templates for the development of more-complex, selective, nontoxic inhibitors of subclass B2 metallo-beta-lactamases.

PubMed: 17307979
DOI: 10.1128/AAC.00866-06

Experimental method

X-RAY DIFFRACTION (1.86 Å)