9CV3

Crystal structure of the metallo-beta-lactamase VIM-20 with L-captopril

Summary for 9CV3

• Entry DOI: 10.2210/pdb9cv3/pdb
• Descriptor: Metallo-beta-lactamase VIM-20, ZINC ION, L-CAPTOPRIL, ... (5 entities in total)
• Functional Keywords: metallo-beta-lactamase, hydrolase
• Biological source: Enterobacter cloacae
• Total number of polymer chains: 1
• Total formula weight: 26475.41

Authors

Silwal, S.B.,Nix, J.C.,Page, R.C. (deposition date: 2024-07-28, release date: 2025-07-09)

Primary citation

Silwal, S.B.,Wamsley, B.,Wang, Z.,Gung, B.W.,Nix, J.C.,Page, R.C.
Mutation of an active site-adjacent residue in VIM indirectly dictates interactions with and blunts inhibition by D-captopril.
J.Inorg.Biochem., 271:112975-112975, 2025

PubMed Abstract: Activity assays and X-ray crystallographic studies were undertaken to elucidate the inhibitory mechanism of captopril stereoisomers on Verona integron-encoded metallo-β-lactamases, specifically VIM-20, VIM-31, and VIM-15. All three VIM-2-like variants (VIM-20, VIM-31, and VIM-15) and VIM-2 expressed in Escherichia coli exhibited catalytic activity with comparable steady-state kinetic parameters. Among the tested thiol drugs (L- and D-captopril, D,L-thiorphan, and 2,3-dimercaprol), IC analyses indicated that D-captopril and 2,3-dimercaprol were more potent inhibitors against the VIM enzymes examined in this study. Notably, the IC value of D-captopril against VIM-31 was an exception, closely resembling that of L-captopril. To elucidate this exceptional inhibitory potency of D-captopril and its binding mode in the active site of VIM-31, high-resolution crystal structures of VIM-20, VIM-31, and VIM-15 in complex with both L- and D-captopril are reported. These findings will help evaluate whether the identified potent inhibitor D-captopril could be further developed as a pan inhibitor targeting the VIM-family enzymes.

PubMed: 40513263
DOI: 10.1016/j.jinorgbio.2025.112975

Experimental method

X-RAY DIFFRACTION (1.51 Å)