Metallo-β-Lactamases: Influence of the Active Site Structure on the Mechanisms of Antibiotic Resistance and Inhibition

The review focuses on bacterial metallo-β-lactamases (MβLs) responsible for the inactivation of β-lactams and associated antibiotic resistance. The diversity of the active site structure in the members of different MβL subclasses explains different mechanisms of antibiotic hydrolysis and should be taken into account when searching for potential MβL inhibitors. The review describes the features of the antibiotic inactivation mechanisms by various MβLs studied by X-ray crystallography, NMR, kinetic measurements, and molecular modeling. The mechanisms of enzyme inhibition for each MβL subclass are discussed.