Moscow University Chemistry Bulletin

, Volume 74, Issue 3, pp 106–110 | Cite as

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

  • M. G. KhrenovaEmail author
  • A. V. Tomilko
  • V. G. Tsirelson


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.


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 [14].


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


  1. 1.
    Mardirossian, N. and Head-Gordon, M., Mol. Phys., 2017, vol. 115, no. 19, p. 2315.CrossRefGoogle Scholar
  2. 2.
    Khrenova, M.G. and Nemukhin, A.V., J. Phys. Chem. B, 2018, vol. 122, no. 4, p. 1378.CrossRefGoogle Scholar
  3. 3.
    Khrenova, M.G., Grigorenko, B.L., Kolomeisky, A.B., and Nemukhin, A.V., J. Phys. Chem. B, 2015, vol. 119, no. 40, p. 12 838.CrossRefGoogle Scholar
  4. 4.
    Khrenova, M.G., Kulakova, A.M., and Nemukhin, A.V., Org. Biomol. Chem., 2018, vol. 16, no. 40, p. 7518.CrossRefGoogle Scholar
  5. 5.
    Liu, S.B., J. Chem. Phys., 2007, vol. 126, 244 103.CrossRefGoogle Scholar
  6. 6.
    von Weizsäcker, C.F., Z. Phys., 1935, vol. 96, p. 431.CrossRefGoogle Scholar
  7. 7.
    Liu, S.B., J. Phys. Chem. A, 2013, vol. 117, no. 5, p. 962.CrossRefGoogle Scholar
  8. 8.
    Wu, W.J., Wu, Z.M., Rong, C.Y., Lu, T., Huang, Y., and Liu, S.B., J. Phys. Chem. A, 2015, vol. 119, no. 29, p. 8216.CrossRefGoogle Scholar
  9. 9.
    Tsirelson, V.G., Stash, A.I., and Liu, S., J. Chem. Phys., 2010, vol. 133, 114 110.CrossRefGoogle Scholar
  10. 10.
    McManus-Munoz, S. and Crowder, M.W., Biochemistry, 1999, vol. 38, no. 5, p. 1547.CrossRefGoogle Scholar
  11. 11.
    Crowder, M.W., Walsh, T.R., Banovic, L., Pettit, M., and Spencer, J., Antimicrob. Agents Chemother., 1998, vol. 42, no. 4, p. 921.CrossRefGoogle Scholar
  12. 12.
    Felici, A. and Amicosante, G., Antimicrob. Agents Chemother., 1995, vol. 39, no. 1, p. 192.CrossRefGoogle Scholar
  13. 13.
    Bader, R.W.F., Atoms in Molecules: A Quantum Theory, Oxford: Clarendon, 1990.Google Scholar
  14. 14.
    Sadovnichy, V., Tikhonravov, A., Voevodin, V., and Opanasenko, V., “Lomonosov”: Supercomputing at Moscow State University, in Contemporary High Performance Computing: From Petascale toward Exascale, Boca Raton: CRC, 2013, p. 283.Google Scholar

Copyright information

© Allerton Press, Inc. 2019

Authors and Affiliations

  • M. G. Khrenova
    • 1
    • 2
    Email author
  • A. V. Tomilko
    • 3
  • V. G. Tsirelson
    • 1
    • 3
  1. 1.Federal Research Centre Fundamentals of Biotechnology, Russian Academy of Sciences,MoscowRussia
  2. 2.Moscow State UniversityMoscowRussia
  3. 3.Mendeleev University of Chemical TechnologyMoscowRussia

Personalised recommendations