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Binding efficiencies of carbohydrate ligands with different genotypes of cholera toxin B: molecular modeling, dynamics and docking simulation studies

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Abstract

Vibrio cholerae produces cholera toxin (CT) that consists of two subunits, A and B, and is encoded by a filamentous phage CTXΦ. The A subunit carries enzymatic activity that ribosylates ADP, whereas the B subunit binds to monosialoganglioside (GM1) receptor in epithelial cells. Molecular analysis of toxigenic V. cholerae strains indicated the presence of multiple ctxB genotypes. In this study, we employed a comparative modeling approach to define the structural features of all known variants of ctxB found in O139 serogroup V. cholerae. Modeling, molecular dynamics and docking simulations studies suggested subtle variations in the binding ability of ctxB variants to carbohydrate ligands of GM1 (galactose, sialic acid and N-acetyl galactosamine). These findings throw light on the molecular efficiencies of pathogenic isolates of V. cholerae harboring natural variants of ctxB in causing the disease, thus suggesting the need to consider ctxB variations when designing vaccines against cholera.

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Acknowledgments

This work was supported in part by a grant from the Indian Council of Medical Research, New Delhi (Immuno. 18/11/17-ECD-I) to DVS and funds contributed by the Department of Biotechnology, New Delhi, to the Institute of Life Sciences. A senior Research Fellowship awarded by the Indian Council of Medical Research, New Delhi, India, to MHU Turabe Fazil is gratefully acknowledged. The authors thank the reviewers for their suggestions.

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Authors and Affiliations

  1. Infectious Disease Biology, Institute of Life Sciences, Nalco Square, Bhubaneswar, 751023, India

    Mobashar Hussain Urf Turabe Fazil & Durg Vijai Singh

  2. Bioinformatics Centre, Institute of Life Sciences, Nalco Square, Bhubaneswar, 751023, India

    Sunil Kumar

  3. Department of Computational Biology and Bioinformatics, Jacob School of Biotechnology and Bioengineering, Sam Higginbottom Institute of Agriculture, Technology and Sciences, Allahabad, 211007, India

    Rohit Farmer

  4. Department of Biochemistry, Faculty of Science, Banaras Hindu University, Varanasi, 221005, India

    Haushila Prasad Pandey

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  1. Mobashar Hussain Urf Turabe Fazil
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Correspondence to Durg Vijai Singh.

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Fazil, M.H.U.T., Kumar, S., Farmer, R. et al. Binding efficiencies of carbohydrate ligands with different genotypes of cholera toxin B: molecular modeling, dynamics and docking simulation studies. J Mol Model 18, 1–10 (2012). https://doi.org/10.1007/s00894-010-0947-6

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  • DOI: https://doi.org/10.1007/s00894-010-0947-6

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