3ho6

Publication Abstract from PubMed

The action of Clostridium difficile toxins A and B depends on inactivation of host small G-proteins by glucosylation. Cellular inositol hexakisphosphate (InsP6) induces an autocatalytic cleavage of the toxins, releasing an N-terminal glucosyltransferase domain into the host cell cytosol. We have defined the cysteine protease domain (CPD) responsible for autoprocessing within toxin A (TcdA) and report the 1.6 A x-ray crystal structure of the domain bound to InsP6. InsP6 is bound in a highly basic pocket that is separated from an unusual active site by a beta-flap structure. Functional studies confirm an intramolecular mechanism of cleavage and highlight specific residues required for InsP6-induced TcdA processing. Analysis of the structural and functional data in the context of sequences from similar and diverse origins highlights a C-terminal extension and a pi-cation interaction within the beta-flap that appear to be unique among the large clostridial cytotoxins.

Structure-function analysis of inositol hexakisphosphate-induced autoprocessing in Clostridium difficile toxin A.,Pruitt RN, Chagot B, Cover M, Chazin WJ, Spiller B, Lacy DB J Biol Chem. 2009 Aug 14;284(33):21934-40. Epub 2009 Jun 24. PMID:19553670^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.