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

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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 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.

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ACKNOWLEDGMENTS

The research is carried out using the equipment of the shared research facilities of HPC computing resources at Lomonosov Moscow State University [14].

Funding

This work was supported by the Russian Science Foundation, project no. 18-74-10056.

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Authors and Affiliations

  1. Federal Research Centre Fundamentals of Biotechnology, Russian Academy of Sciences,, 119071, Moscow, Russia

    M. G. Khrenova & V. G. Tsirelson

  2. Moscow State University, 119899, Moscow, Russia

    M. G. Khrenova

  3. Mendeleev University of Chemical Technology, 125190, Moscow, Russia

    A. V. Tomilko & V. G. Tsirelson

Authors
  1. M. G. Khrenova
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  2. A. V. Tomilko
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  3. V. G. Tsirelson
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Correspondence to M. G. Khrenova.

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Translated by M. Novikova

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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. Moscow Univ. Chem. Bull. 74, 106–110 (2019). https://doi.org/10.3103/S0027131419030076

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  • DOI: https://doi.org/10.3103/S0027131419030076

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