3ho6
Structure-function analysis of inositol hexakisphosphate-induced autoprocessing in clostridium difficile toxin AStructure-function analysis of inositol hexakisphosphate-induced autoprocessing in clostridium difficile toxin A
Structural highlights
Function[TOXA_PEPDI] Only after the enteral delivery of the enterotoxin A may the characteristic disease called pseudomembranous colitis be induced. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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. References
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