4C1E: Crystal structure of the metallo-beta-lactamase VIM-2 with D-captopril

Citation:
Abstract
beta-Lactams are the most successful antibacterials, but their effectiveness is threatened by resistance, most importantly by production of serine- and metallo-beta-lactamases (MBLs). MBLs are of increasing concern because they catalyze the hydrolysis of almost all beta-lactam antibiotics, including recent-generation carbapenems. Clinically useful serine-beta-lactamase inhibitors have been developed, but such inhibitors are not available for MBLs. l-Captopril, which is used to treat hypertension via angiotensin-converting enzyme inhibition, has been reported to inhibit MBLs by chelating the active site zinc ions via its thiol(ate). We report systematic studies on B1 MBL inhibition by all four captopril stereoisomers. High-resolution crystal structures of three MBLs (IMP-1, BcII, and VIM-2) in complex with either the l- or d-captopril stereoisomer reveal correlations between the binding mode and inhibition potency. The results will be useful in the design of MBL inhibitors with the breadth of selectivity required for clinical application against carbapenem-resistant Enterobacteriaceae and other organisms causing MBL-mediated resistant infections.
PDB ID: 4C1EDownload
MMDB ID: 122662
PDB Deposition Date: 2013/8/12
Updated in MMDB: 2015/11
Experimental Method:
x-ray diffraction
Resolution: 1.399  Å
Source Organism:
Similar Structures:
Biological Unit for 4C1E: monomeric; determined by author and by software (PISA)
Molecular Components in 4C1E
Label Count Molecule
Protein (1 molecule)
1
Beta-lactamase Class B Vim-2
Molecule annotation
Chemicals (8 molecules)
1
1
2
1
3
3
4
3
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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