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| Content Provider | Springer Nature Link |
|---|---|
| Author | Prisilla, A. Prathiviraj, R. Chellapandi, P. |
| Copyright Year | 2017 |
| Abstract | Clostridium botulinum (group-III) is an anaerobic bacterium producing C2 toxin along with botulinum neurotoxins. C2 toxin is belonged to binary toxin A family in bacterial ADP-ribosylation superfamily. A structural and functional diversity of binary toxin A family was inferred from different evolutionary constraints to determine the avirulence state of C2 toxin. Evolutionary genetic analyses revealed evidence of C2 toxin cluster evolution through horizontal gene transfer from the phage or plasmid origins, site-specific insertion by gene divergence, and homologous recombination event. It has also described that residue in conserved NAD-binding core, family-specific domain structure, and functional motifs found to predetermine its virulence state. Any mutational changes in these residues destabilized its structure–function relationship. Avirulent mutants of C2 toxin were screened and selected from a crucial site required for catalytic function of C2I and pore-forming function of C2II. We found coevolved amino acid pairs contributing an essential role in stabilization of its local structural environment. Avirulent toxins selected in this study were evaluated by detecting evolutionary constraints in stability of protein backbone structure, folding and conformational dynamic space, and antigenic peptides. We found 4 avirulent mutants of C2I and 5 mutants of C2II showing more stability in their local structural environment and backbone structure with rapid fold rate, and low conformational flexibility at mutated sites. Since, evolutionary constraints-free mutants with lack of catalytic and pore-forming function suggested as potential immunogenic candidates for treating C. botulinum infected poultry and veterinary animals. Single amino acid substitution in C2 toxin thus provides a major importance to understand its structure–function link, not only of a molecule but also of the pathogenesis. |
| Starting Page | 174 |
| Ending Page | 186 |
| Page Count | 13 |
| File Format | |
| ISSN | 00222844 |
| Journal | Journal of Molecular Evolution |
| Volume Number | 84 |
| Issue Number | 4 |
| e-ISSN | 14321432 |
| Language | English |
| Publisher | Springer US |
| Publisher Date | 2017-04-05 |
| Publisher Place | New York |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Binary toxin A ADP ribosyltransferase Site-directed mutagenesis Molecular dynamics Coevolution Evolutionary Biology Microbiology Plant Sciences Plant Genetics & Genomics Animal Genetics and Genomics Cell Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Molecular Biology Ecology, Evolution, Behavior and Systematics |
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