Structure–function discrepancy in Clostridium botulinum C3 toxin for its rational prioritization as a subunit vaccine

Physiological group III strains (type C and D) of this bacterium are capable of producing C2 and C3 toxins in cattle and avian. Herein, we have revealed the structure–function disparity of C3 toxins from two different C. botulinum type C phage (CboC) and type D phage (CboD) to design avirulent toxins rationally.

Structure–function discrepancy of the both toxins was computationally evaluated from their homology models based on the conservation in sequence–structure–function relationships upon covariation and point mutations. It has shown that 8 avirulent mutants were generated from CboC of 34 mutants while 27 avirulent mutants resulted from CboD mutants. No major changes were found in tertiary structure of these toxins; however, some structural variations appeared in the coiled and loop regions.