Biapenem inactivation by B2 metallo β-lactamases: energy landscape of the post-hydrolysis reactions.

ABSTRACT:

Background

The first line of defense by bacteria against β-lactam antibiotics is the expression of β-lactamases, which cleave the amide bond of the β-lactam ring. In the reaction of biapenem inactivation by B2 metallo β-lactamases (MβLs), after the β-lactam ring is opened, the carboxyl group generated by the hydrolytic process and the hydroxyethyl group (common to all carbapenems) rotate around the C5-C6 bond, assuming a new position that allows a proton transfer from the hydroxyethyl group to C2, and a nucleophilic attack on C3 by the oxygen atom of the same side-chain. This process leads to the formation of a bicyclic compound, as originally observed in the X-ray structure of the metallo β-lactamase CphA in complex with product.

Methodology/principal findings

QM/MM and met

SUBMITTER: Gatti DL 

PROVIDER: S-EPMC3260057 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature