A theoretical approach for the acylation/deacylation mechanisms of avibactam in the reversible inhibition of KPC-2.

ABSTRACT: Klebsiella pneumoniae carbapenemase (KPC-2) is the most commonly encountered class A β-lactamase variant worldwide, which confer high-level resistance to most available antibiotics. In this article we address the issue by a combined approach involving molecular dynamics simulations and hybrid quantum mechanics/molecular mechanics calculations. The study contributes to improve the understanding, at molecular level, of the acylation and deacylation stages of avibactam involved in the inhibition of KPC-2. The results show that both mechanisms, acylation and deacylation, the reaction occur via the formation of a tetrahedral intermediate. The formation of this intermediate corresponds to the rate limiting stage. The activation barriers are 19.5 kcal/mol and 23.0 kcal/mol for the acylation and d

SUBMITTER: Lizana I 

PROVIDER: S-EPMC8264174 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature