1GYG

R32 CLOSED FORM OF ALPHA-TOXIN FROM CLOSTRIDIUM PERFRINGENS STRAIN CER89L43

Summary for 1GYG

• Entry DOI: 10.2210/pdb1gyg/pdb
• Related: 1CA1 1QM6 1QMD
• Descriptor: PHOSPHOLIPASE C, ZINC ION (3 entities in total)
• Functional Keywords: zinc phospholipase c, gangrene determinant, c2 domain, ca and membrane binding, hydrolase
• Biological source: CLOSTRIDIUM PERFRINGENS
• Total number of polymer chains: 2
• Total formula weight: 85493.36

Authors

Basak, A.K.,Eaton, J.T.,Titball, R.W. (deposition date: 2002-04-23, release date: 2002-06-13, Last modification date: 2024-05-01)

Primary citation

Eaton, J.T.,Naylor, C.,Howells, A.,Moss, D.,Titball, R.W.,Basak, A.K.
Crystal Structure of the C. Perfringens Alpha-Toxin with the Active Site Closed by a Flexible Loop Region
J.Mol.Biol., 319:275-, 2002

PubMed Abstract: Clostridium perfringens biotype A strains are the causative agents of gas-gangrene in man and are also implicated as etiological agents in sudden death syndrome in young domestic livestock. The main virulence factor produced by these strains is a zinc-dependent, phosphatidylcholine-preferring phospholipase C (alpha-toxin). The crystal structure of alpha-toxin, at pH 7.5, with the active site open and therefore accessible to substrate has previously been reported, as has calcium-binding to the C-terminal domain of the enzyme at pH 4.7. Here we focus on conformation changes in the N-terminal domain of alpha-toxin in crystals grown at acidic pH. These changes result in both the obscuring of the toxin active site and the loss of one of three zinc ions from it. Additionally, this "closed" form contains a small alpha helix, not present in the open structure, which hydrogen bonds to both the N and C-terminal domains. In conjunction with the previously reported findings that alpha-toxin can exist in active and inactive forms and that Thr74Ile and Phe69Cys substitutions markedly reduced the haemolytic activity of the enzyme, our work suggests that these loop conformations play a critical role in the activity of the toxin.

PubMed: 12051905
DOI: 10.1016/S0022-2836(02)00290-5

Experimental method

X-RAY DIFFRACTION (1.9 Å)