Beyond structure and activity: targeting class A carbapenemases with monocyclic and bicyclic boronic acids to counter antimicrobial resistance

Abstract

Bicyclic boronic acids inhibit SME-1 carbapenemase via a unique π–π stacking with His105 and covalent interaction with Ser70. Ledaborbactam shows the strongest inhibition, with the lowest k_i and enhanced structural stability. X-ray crystallography and molecular dynamics reveal key features helpful in structure-based optimization of boronates targeting class A β-lactamases.