Structure of the key toxin in gas gangrene
Clostridium perfringens alpha-toxin is the key virulence determinant in gas gangrene and has also been implicated in the pathogenesis of sudden death syndrome in young animals. The toxin is a 370-residue, zinc metalloenzyme that has phospholipase C activity, and can bind to membranes in the presence...
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| Veröffentlicht in: | Nature structural & molecular biology 1998-08, Vol.5 (8), p.738-746 |
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| creator | Naylor, C E Eaton, J T Howells, A Justin, N Moss, D S Titball, R W Basak, A K |
| description | Clostridium perfringens alpha-toxin is the key virulence determinant in gas gangrene and has also been implicated in the pathogenesis of sudden death syndrome in young animals. The toxin is a 370-residue, zinc metalloenzyme that has phospholipase C activity, and can bind to membranes in the presence of calcium. The crystal structure of the enzyme reveals a two-domain protein. The N-terminal domain shows an anticipated structural similarity to Bacillus cereus phosphatidylcholine-specific phospholipase C (PC-PLC). The C-terminal domain shows a strong structural analogy to eukaryotic calcium-binding C2 domains. We believe this is the first example of such a domain in prokaryotes. This type of domain has been found to act as a phospholipid and/or calcium-binding domain in intracellular second messenger proteins and, interestingly, these pathways are perturbed in cells treated with alpha-toxin. Finally, a possible mechanism for alpha-toxin attack on membrane-packed phospholipid is described, which rationalizes its toxicity when compared to other, non-haemolytic, but homologous phospholipases C. |
| doi_str_mv | 10.1038/1447 |
| format | Article |
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The toxin is a 370-residue, zinc metalloenzyme that has phospholipase C activity, and can bind to membranes in the presence of calcium. The crystal structure of the enzyme reveals a two-domain protein. The N-terminal domain shows an anticipated structural similarity to Bacillus cereus phosphatidylcholine-specific phospholipase C (PC-PLC). The C-terminal domain shows a strong structural analogy to eukaryotic calcium-binding C2 domains. We believe this is the first example of such a domain in prokaryotes. This type of domain has been found to act as a phospholipid and/or calcium-binding domain in intracellular second messenger proteins and, interestingly, these pathways are perturbed in cells treated with alpha-toxin. 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| source | MEDLINE; Nature; Springer Nature - Complete Springer Journals |
| subjects | Amino Acid Sequence Bacterial Toxins - chemistry Bacterial Toxins - metabolism Binding Sites Calcium - metabolism Calcium-Binding Proteins - chemistry Calcium-Binding Proteins - metabolism Clostridium perfringens Clostridium perfringens - pathogenicity Computer Simulation Crystallography Gas Gangrene Hemolysin Proteins - chemistry Humans Male Membranes - metabolism Metalloproteins - chemistry Metalloproteins - metabolism Models, Molecular Molecular Sequence Data Protein Binding Protein Conformation Second Messenger Systems Sequence Homology, Amino Acid Synchrotrons Type C Phospholipases - chemistry Type C Phospholipases - metabolism Zinc |
| title | Structure of the key toxin in gas gangrene |
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