Common mechanistic features among metallo-beta-lactamases: a computational study of Aeromonas hydrophila CphA enzyme.

ABSTRACT: Metallo-beta-lactamases (MbetaLs) constitute an increasingly serious clinical threat by giving rise to beta-lactam antibiotic resistance. They accommodate in their catalytic pocket one or two zinc ions, which are responsible for the hydrolysis of beta-lactams. Recent x-ray studies on a member of the mono-zinc B2 MbetaLs, CphA from Aeromonas hydrophila, have paved the way to mechanistic studies of this important subclass, which is selective for carbapenems. Here we have used hybrid quantum mechanical/molecular mechanical methods to investigate the enzymatic hydrolysis by CphA of the antibiotic biapenem. Our calculations describe the entire reaction and point to a new mechanistic description, which is in agreement with the available experimental evidence. Within our proposal, the zinc ion pr

SUBMITTER: Simona F 

PROVIDER: S-EPMC2788867 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature