title: Binding efficiencies of carbohydrate ligands with different genotypes of cholera toxin B: molecular modeling, dynamics and docking simulation studies.
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.
authors.affiliation: Infectious Disease Biology, Institute of Life Sciences, Nalco Square, Bhubaneswar, India.
authors.forename: Mobashar Hussain Urf Turabe
authors.initials: MH
authors.lastname: Fazil
authors.forename: Sunil
authors.initials: S
authors.lastname: Kumar
authors.forename: Rohit
authors.initials: R
authors.lastname: Farmer
authors.forename: Haushila Prasad
authors.initials: HP
authors.lastname: Pandey
authors.forename: Durg Vijai
authors.initials: DV
authors.lastname: Singh
mesh_terms: D001483:Base Sequence; D050260:Carbohydrate Metabolism; D002241:Carbohydrates / Q000737:chemistry*; D002772:Cholera Toxin / Q000737:chemistry* / Q000235:genetics; D004269:DNA, Bacterial / Q000032:analysis / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D014644:Genetic Variation; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D017422:Sequence Analysis, DNA; D014734:Vibrio cholerae / Q000378:metabolism / Q000472:pathogenicity
chemical_list: D002241:Carbohydrates; D004269:DNA, Bacterial; D002772:Cholera Toxin