Electronic Steric Factors in the Active Site of Metallo-β-Lactamase and Reactivity of Cephalosporin Antibiotics
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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 kcat) 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.
Keywords:cephalosporin antibiotics metallo-β-lactamases hydrolysis QM/MM electronic steric effects steric energy
The research is carried out using the equipment of the shared research facilities of HPC computing resources at Lomonosov Moscow State University .
This work was supported by the Russian Science Foundation, project no. 18-74-10056.
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