Boronic Acids as Prospective Inhibitors of Metallo-β-Lactamases: Efficient Chemical Reaction in the Enzymatic Active Site Revealed by Molecular Modeling.

ABSTRACT: Boronic acids are prospective compounds in inhibition of metallo-β-lactamases as they form covalent adducts with the catalytic hydroxide anion in the enzymatic active site upon binding. We compare this chemical reaction in the active site of the New Delhi metallo-β-lactamase (NDM-1) with the hydrolysis of the antibacterial drug imipenem. The nucleophilic attack occurs with the energy barrier of 14 kcal/mol for imipenem and simultaneously upon binding a boronic acid inhibitor. A boron atom of an inhibitor exhibits stronger electrophilic properties than the carbonyl carbon atom of imipenem in a solution that is quantified by atomic Fukui indices. Upon forming the prereaction complex between NDM-1 and inhibitor, the lone electron pair of the nucleophile interacts with the vacant p-orbi

SUBMITTER: Krivitskaya AV 

PROVIDER: S-EPMC8038151 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature