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Khrenova M. G., Tomilko A. V., Tsirelson V. G.
Electronic steric factors in the active
site of metallo-β-lactamase and reactivity of
cephalosporin antibiotics
Abstract
The paper presents the results of the study
of the relationship of electronic steric factors in the active site of metallo-β-lactamase and reactivity of cephalosporin antibiotics. 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 kinetics of Michaelis-Menten – catalytic constant kcat
is proposed: the increase in the rate constant is associated with an increase
in steric energy. Two-dimensional maps of steric potential and steric energy
density are analyzed.
Key words: cephalosporin antibiotics,
metallo--lactamases, hydrolysis, QM/MM,
electronic steric effects, steric energy.
Copyright (C) Chemistry Dept., Moscow State University, 2002
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