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Molecular modeling of ceftriaxone activation in the active sites of penicillin-binding proteins 2

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Abstract

The enzyme—substrate complexes of penicillin-binding proteins PBP2 from FA19, 35/02, and H041 strains of Nisseria gonorrhoeae with ceftriaxone were simulated by the molecular dynamics method with the combined quantum mechanics/molecular mechanics potentials. The hydrogen bond lengths between the carbonyl oxygen atom of the substrate and amino acid residues of the oxyanion hole, as well as the distances of the nucleophilic attack by the oxygen atom of the catalytic serine of the carbonyl carbon atom of the substrate were considered. The 2D maps of the Laplacian of electron density show a more efficient activation of the substrate by the wild type enzyme rather than mutated species. This is consistent with the geometry features: distributions of the lengths of hydrogen bonds forming oxyanion hole and nucleophilic attack distance that are shifted toward lower values.

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Authors and Affiliations

  1. A. N. Bach Institute of Biochemistry, Federal Research Centre “Fundamentals of Biotechnology” of the Russian Academy of Sciences, Build. 2, 33 Leninsky prosp., 119071, Moscow, Russian Federation

    A. V. Krivitskaya & M. G. Khrenova

  2. Department of Chemistry, Lomonosov Moscow State University, Build. 3, 1 Leninskie Gory, 119991, Moscow, Russian Federation

    M. G. Khrenova

Authors
  1. A. V. Krivitskaya
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  2. M. G. Khrenova
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Correspondence to M. G. Khrenova.

Additional information

Based on the materials of the XXXIII Symposium “Modern Chemical Physics” (September 24–October 4, 2021, Tuapse, Russia).

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 915–920, May, 2022.

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

This work was financially supported by the Russian Science Foundation (Project No. 18-74-10056).

No human or animal subjects were used in this research.

The authors declare no competing interests.

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Krivitskaya, A.V., Khrenova, M.G. Molecular modeling of ceftriaxone activation in the active sites of penicillin-binding proteins 2. Russ Chem Bull 71, 915–920 (2022). https://doi.org/10.1007/s11172-022-3490-6

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  • DOI: https://doi.org/10.1007/s11172-022-3490-6

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