Structural inferences for Cholera toxin mutations in Vibrio cholerae 


Gunasagaran Shamini1, 5, Manickam Ravichandran1, John T Sinnott2, 3, Charurut Somboonwit2, 3, Harcharan S Siddhu1, Paul Shapshak2, 4, Pandjassarame Kangueane1, 5* 


1Department of Biotechnology, AIMST University, Semeling 08100, Kedah, Malaysia; 2Division of Infectious Disease, Department of Internal Medicine, Tampa General Hospital, University of South Florida, College of Medicine, Tampa, Florida 33606, USA; 3Clinical Research Unit, Hillsborough Health Department, Tampa, Florida 33602, USA; 4Department of Psychiatry and Behavioral Medicine, University of South Florida, College of Medicine, Tampa, Florida 33613, USA; 5Biomedical Informatics, Pondicherry, India 607402  

Email; *Corresponding author  


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Article Type




Received January 20, 2011; Accepted February 01, 2011; Published March 02, 2011


Cholera is a global disease that has persisted for millennia. The cholera toxin (CT) from Vibrio cholerae is responsible for the clinical symptoms of cholera. This toxin is a hetero-hexamer (AB5) complex consisting of a subunit A (CTA) with a pentamer (B5) of subunit B (CTB). The importance of the AB5 complex for pathogenesis is established for the wild type O1 serogroup using known structural and functional data. However, its role is not yet documented in other known serogroups harboring sequence level residue mutations. The sequences for the toxin from different serogroups are available in GenBank (release 177). Sequence analysis reveals mutations at several sequence positions in the toxin across serogroups. Therefore, it is of interest to locate the position of these mutations in the AB5 structure to infer complex assembly for its functional role in different serogroups. We show that mutations in the CTA are at the solvent exposed regions of the AB5 complex, whereas those in the CTB are at the CTB/CTB interface of the homo-pentamer complex. Thus, the role of mutations at the CTB/CTB interface for B5 complex assembly is implied. It is observed that these mutations are often non-synonymous (e.g. polar to non-polar or vice versa). The formation of the AB5 complex involves inter-subunit residue-residue interactions at the protein-protein interfaces. Hence, these mutations, at the structurally relevant positions, are of importance for the understanding of pathogenesis by several serogroups. This is also of significance in the improvement of recombinant CT protein complex analogs for vaccine design and their use against multiple serogroups. 


Cholera toxin (CT), Vibrio cholerae, O1/O139, non O1/O139, mutation, protein-protein interfaces


Shamini et al. Bioinformation 6(1): 1- 9 (2011)

Edited by

VS Mathura






Biomedical Informatics



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