Mechanism of Metallo-β-Lactamase Inhibition by Oxacephalosporin Antibiotic

Metallo-β-lactamases is a family of bacterial zinc-dependent enzymes that hydrolyze β-lactam antibiotics and are responsible for the bacterial resistance to them. As a result of the reaction, the slowly hydrolyzed substrate moxalactam undergoes not only chemical transformations in the structure of the β-lactam ring but a negatively charged fragment is also released on the periphery of the molecule, resulting in the formation of an intermediate firmly bound to the active site. In the paper, we present the results of the calculations of the mechanism of this process by a combined quantum mechanics/molecular mechanics approach.