Theoretical Evidence for the Nonoccurrence of Tetrahedral Intermediates in the Deacylation Pathway of the Oxacillinase-24/Avibactam Complex.

ABSTRACT: Oxacillinases (OXAs) β-lactamases are of special interest because of their capacity to hydrolyze antibacterial drugs such as cephalosporins and carbapenems, which are frequently used as the last option for the treatment of multidrug-resistant bacteria. Although the comprehension of the involved mechanisms at the atomic level is crucial for the rational design of new inhibitors and antibiotics, currently there is no study on the acylation/deacylation mechanisms of the OXA-24/avibactam complex from first principles; therefore, mechanistic details such as activation barriers, characterization of intermediates, and transition states are still uncertain. In this article, we address the deacylation of the OXA-24/avibactam complex by molecular dynamics simulations and hybrid quantum mechanics/mol

SUBMITTER: Lizana I 

PROVIDER: S-EPMC6933777 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature