Electronic Steric Factors in the Active Site of Metallo-β-Lactamase and Reactivity of Cephalosporin Antibiotics

Abstract

In this paper, the relationship of electronic steric factors in the active site of metallo-β-lactamase and reactivity of cephalosporin antibiotics is studied. The steric energy of the oxygen atom forming a temporary covalent bond in the structure of the transition state of the limiting stage characterizes the reactivity of the compounds. A linear relationship between this value and the macroscopic parameter of the stationary Michaelis–Menten kinetics (catalytic constant k_cat) is proposed: the increase in the rate constant is associated with an increase in steric energy. Two-dimensional maps of the steric potential and steric energy density are analyzed.