Comparison of a nontoxic variant of Clostridium perfringens alpha-toxin with the toxic wild-type strain
Vachieri, S.G. and Clark, G.C. and Alape-Giron, A. and Flores-Diaz, M. and Justin, N. and Naylor, Claire E. and Titball, R.W. and Basak, Ajit K. (2010) Comparison of a nontoxic variant of Clostridium perfringens alpha-toxin with the toxic wild-type strain. Acta Crystallographica Section D Biological Crystallography D66 , pp. 1067-1074. ISSN 0907-4449.
The alpha-toxin produced by Clostridium perfringens is one of the best-studied examples of a toxic phospholipase C. In this study, a nontoxic mutant protein from C. perfringens strain NCTC8237 in which Thr74 is substituted by isoleucine (T74I) has been characterized and is compared with the toxic wild-type protein. Thr74 is part of an exposed loop at the proposed membrane-interfacing surface of the toxin. The mutant protein had markedly reduced cytotoxic and myotoxic activities. However, this substitution did not significantly affect the catalytic activity towards water-soluble substrate or the overall three-dimensional structure of the protein. The data support the proposed role of the 70-90 loop in the recognition of membrane phospholipids. These findings also provide key evidence in support of the hypothesis that the hydrolysis of both phosphatidylcholine and sphingomyelin are required for the cytolytic and toxic activity of phospholipases.
|Keyword(s) / Subject(s):||phospholipase C, clostridium perfringens, toxicity|
|School:||Birkbeck Schools and Departments > School of Science > Biological Sciences|
|Date Deposited:||09 Jun 2011 14:16|
|Last Modified:||17 Apr 2013 12:20|
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