'''CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF LETHAL TOXIN FROM CLOSTRIDIUM SORDELLII IN COMPLEX WITH UDP-GLC AND CALCIUM ION'''
===CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF LETHAL TOXIN FROM CLOSTRIDIUM SORDELLII IN COMPLEX WITH UDP-GLC AND CALCIUM ION===
==Overview==
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The crystal structures of the catalytic fragments of 'lethal toxin' from Clostridium sordellii and of 'alpha-toxin' from Clostridium novyi have been established. Almost half of the residues follow the chain fold of the glycosyl-transferase type A family of enzymes; the other half forms large alpha-helical protrusions that are likely to confer specificity for the respective targeted subgroup of Rho proteins in the cell. In the crystal, the active center of alpha-toxin contained no substrates and was disassembled, whereas that of lethal toxin, which was ligated with the donor substrate UDP-glucose and cofactor Mn(2+), was catalytically competent. Surprisingly, the structure of lethal toxin with Ca(2+) (instead of Mn(2+)) at the cofactor position showed a bound donor substrate with a disassembled active center, indicating that the strictly octahedral coordination sphere of Mn(2+) is indispensable to the integrity of the enzyme. The homologous structures of alpha-toxin without substrate, distorted lethal toxin with Ca(2+) plus donor, active lethal toxin with Mn(2+) plus donor and the homologous Clostridium difficile toxin B with a hydrolyzed donor have been lined up to show the geometry of several reaction steps. Interestingly, the structural refinement of one of the three crystallographically independent molecules of Ca(2+)-ligated lethal toxin resulted in the glucosyl half-chair conformation expected for glycosyl-transferases that retain the anomeric configuration at the C1'' atom. A superposition of six acceptor substrates bound to homologous enzymes yielded the position of the nucleophilic acceptor atom with a deviation of <1 A. The resulting donor-acceptor geometry suggests that the reaction runs as a circular electron transfer in a six-membered ring, which involves the deprotonation of the nucleophile by the beta-phosphoryl group of the donor substrate UDP-glucose.
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{{ABSTRACT_PUBMED_18325534}}
==About this Structure==
==About this Structure==
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[[Category: Glycosyltransferase]]
[[Category: Glycosyltransferase]]
[[Category: Toxin]]
[[Category: Toxin]]
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Revision as of 14:02, 28 July 2008
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