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Proposed Mechanism of Antibacterial Activity of Glutathione by Inhibition of the d-Alanyl-d-alanine Carboxypeptidase Enzyme

International Journal of Peptide Research and Therapeutics Aims and scope Submit manuscript

Abstract

Several reports have suggested that glutathione (GSH) has antibacterial activity. However, the mechanism by which GSH inhibits microbial growth is a mystery. GSH has a structure similar to the antibiotic precursors of Penicillium that work as inhibitors of the d-alanyl-d-alanine-carboxypeptidase (DacC) enzyme. DacC catalyzes glycopeptides (d-alanyl-alanine) to form peptidoglycan in cell walls. Our objective was to study the potential mechanism of GSH as an inhibitor of the DacC enzyme in silico. Then, its activity that inhibited the growth of Salmonella typhi in vitro was tested. The binding affinity between GSH and DacC was examined by molecular docking. The pharmacophore of GSH was evaluated by Molinspiration and SwissADME. The stability of the GSH–DacC complex was measured by molecular dynamics, whereas antibacterial activity was examined by the disk diffusion and dilution methods, and then by scanning electron microscopy. The results indicate that GSH has the same ability as ampicillin in binding to the active site of DacC. GSH is capable of inhibiting the growth of S. typhi in vitro and is even known to cause cell wall damage. absorption, distribution, metabolism, and excretion predictions indicate that the properties of GSH are comparable to those of ampicillin. GSH is assumed to exert antibacterial activity by inhibiting the DacC enzyme, which might inhibit bacterial cell wall synthesis.

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Acknowledgements

We would like to express our gratitude to Lembaga Pengelola Dana Pendidikan, and the Ministry of Finance Indonesia for the BUDI-DN scholarship supporting our study.

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Authors and Affiliations

  1. Doctoral Program of Biology, Faculty of Mathematics and Natural Science, Brawijaya University, Malang, Indonesia

    Dewi Mustikaningtyas

  2. Biology Department, Faculty of Mathematics and Natural Science, Brawijaya University, Malang, Indonesia

    Sri Widyarti, Muhaimin Rifa’i & Nashi Widodo

  3. Biology Department, Faculty of Mathematics and Natural Science, Universitas Negeri Semarang, Semarang, Indonesia

    Dewi Mustikaningtyas

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  1. Dewi Mustikaningtyas
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  2. Sri Widyarti
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Correspondence to Sri Widyarti.

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Mustikaningtyas, D., Widyarti, S., Rifa’i, M. et al. Proposed Mechanism of Antibacterial Activity of Glutathione by Inhibition of the d-Alanyl-d-alanine Carboxypeptidase Enzyme. Int J Pept Res Ther 27, 843–849 (2021). https://doi.org/10.1007/s10989-020-10124-5

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