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    Binding of Metronidazole to Enterococcus faecalis Homoserine Kinase: Binding Studies, Docking Studies, and Molecular Dynamics Simulation Studies

    Harpreet Singh1, Satyajeet Das1, Pramodkumar P Gupta2, Sagar Batra1, Richa Prakash1, Vijay Kumar Srivastava1, Anupam Jyoti1, Vikas Gupta3, S. L. Kothari1, Sanket Kaushik1★★ Corresponding author

    1. 1Amity Institute of Biotechnology, Amity University, Jaipur, Rajasthan, India.
    2. 2School of Biotechnology and Bioinformatics, DY Patil Deemed to be University, Navi Mumbai, Maharashtra, India.
    3. 3Department of Biotechnology, DAV College, Amritsar, Punjab, India.

    CORRESPONDENCE

    Sanket Kaushik

    Amity Institute of Biotechnology, Amity University, Jaipur, Rajasthan, India.

    sanketkaushik@gmail.com

    Received: 13-03-2020; Revised: 05-05-2020; Accepted: 06-07-2020.

    Volume 16, Issue 5S · pp. S553–S560 · PUBLISHED 30 November 2020 · DOI: 10.4103/pm.pm_99_20

    View on Pharmacogn. Mag. original site ↗

    ABSTRACT

    Objective: Looking at the increasing number of infections caused by Ef, it is essential to develop alternative strategies to fight against Ef. In this regard, homoserine kinase (HSK) is an important enzyme of threonine biosynthesis pathway in Ef. Threonine is an essential amino acid, and HSK catalyzes the formation of O‑phospho‑L‑homoserine production, which is an important step in threonine metabolism. Therefore, Enterococcus faecalis homoserine kinase (EfHSK) becomes an ideal target for antimicrobial drug development. Methodology: We report binding studies, docking studies, and molecular dynamics (MD) simulation studies of EfHSK. Fluorescence spectroscopy studies indicated the binding of metronidazole with EfHSK. Result: Docking studies further showed that amino acid residues such as Asn124 and Gly83 in the phosphate‑binding loop of EfHSK play a vital role in the formation of H‑bonds with the ligand metronidazole. The site where ligand was bound is a deep groove, which is regarded as the binding cavity of the protein. Docking studies were further confirmed by MD simulation studies. Conclusion: Metronidazole might be considered as a potential inhibitor of EfHSK, as this occupies the binding pocket and eventually can reduce the kinase activity of this enzyme.

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      Singh, H., Das, S., Gupta, P. P., Batra, S., Prakash, R., Srivastava, V. K., Jyoti, A., Gupta, V., Kothari, S. L., & Kaushik, S. (2020). Binding of Metronidazole to Enterococcus faecalis Homoserine Kinase: Binding Studies, Docking Studies, and Molecular Dynamics Simulation Studies. Pharmacognosy Magazine, 16(5S), S553–S560. https://doi.org/10.4103/pm.pm_99_20