2GKL: Crystal Structure Of The Zinc Carbapenemase Cpha In Complex With The Inhibitor Pyridine-2,4-Dicarboxylate

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.
PDB ID: 2GKLDownload
MMDB ID: 44975
PDB Deposition Date: 2006/4/3
Updated in MMDB: 2012/10
Experimental Method:
x-ray diffraction
Resolution: 1.86  Å
Source Organism:
Similar Structures:
Biological Unit for 2GKL: monomeric; determined by author and by software (PISA)
Molecular Components in 2GKL
Label Count Molecule
Protein (1 molecule)
Molecule annotation
Chemicals (5 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB