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Molecular Model of Norfloxacin Translocation through Yersinia pseudotuberculosis Porin OmpF Channel: Electrophysiological and Molecular Modeling Study

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Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Aims and scope

Abstract—

The interaction of the Yersinia pseudotuberculosis porin OmpF (YpOmpF) with the fluoroquinolone antibiotic norfloxacin (Nf) and its derivatives (mono- and dihydrochloride) was studied using the bilayer lipid membrane (BLM) method, molecular modeling, and antibacterial activity testing. An asymmetric behavior of the Nf charged molecules was found: NfH+1 and Nf2H+2 moved through the YpOmpF channel, depending on the membrane voltage and on the side where the antibiotic was added. The electrophysiological data were confirmed by computational modeling. For charged forms of the antibiotic, the presence of two peripheral high-affinity binding sites (NBS1 and NBS2), as well as an asymmetric current blocking site (NBS3) near the channel constriction zone were detected. The NBS1 site located near the channel mouth has almost the same affinity for both charged forms of Nf, while the localization of the more energetically favorable NBS2 site for the two salt forms of the antibiotic differs significantly. Nf has only one binding site near the constriction zone, which is a cluster of sites with a lower overall affinity compared to the peripheral binding sites mentioned above. Slight differences were found in the antibacterial activity of the three forms of Nf, which is likely due to their different charge states and, accordingly, different permeability and/or ability to bind within the YpOmpF channel.

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ACKNOWLEDGMENTS

The authors are grateful to Dr. Sci. Dmitry Aminin for review and valuable comments, and Ph.D. Viktoria Davydova for fruitful discussion. Computer simulation and theoretical studies were performed using cluster CCU “Far Eastern computing resource” FEB RAS (Vladivostok).

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State assignment, topic No. AAAA-A20-120011490018-3.

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Authors and Affiliations

  1. G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 690022, Vladivostok, Russia

    D. K. Chistyulin, E. A. Zelepuga, V. L. Novikov, N. N. Balaneva, V. P. Glazunov, E. A. Chingizova, V. A. Khomenko & O. D. Novikova

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  1. D. K. Chistyulin
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  2. E. A. Zelepuga
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Contributions

Conceptualization, O.N., E.Z., and V.N.; methodology, V.N., D.Ch., E.Z., and V.Kh; formal analysis, V.N., D.Ch., E.Z., E.Ch.; investigation, D.Ch., E.Z., E.Ch., N.B., V.N., V.G., and V.Kh; data curation, O.N., E.Z., and V.N; writing, original draft preparation, O.N, D.Ch., V.N., and E.Z.; writing, review and editing, O.N, V.N., and E.Z.; visualization, D.Ch., E.Z., and N.B.; supervision, O.N. All authors have read and agreed to the published version of the manuscript. Authors D. Ch. and E.Z. contributed equally to this work and share first authorship.

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Translated by O. Novikova, E. Zelepuga and V. Novikov

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Chistyulin, D.K., Zelepuga, E.A., Novikov, V.L. et al. Molecular Model of Norfloxacin Translocation through Yersinia pseudotuberculosis Porin OmpF Channel: Electrophysiological and Molecular Modeling Study. Biochem. Moscow Suppl. Ser. A 17 (Suppl 1), S20–S38 (2023). https://doi.org/10.1134/S1990747823070024

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