3HO6

Structure-function analysis of inositol hexakisphosphate-induced autoprocessing in clostridium difficile toxin A

Summary for 3HO6

• Entry DOI: 10.2210/pdb3ho6/pdb
• Descriptor: Toxin A, INOSITOL HEXAKISPHOSPHATE (3 entities in total)
• Functional Keywords: inositol phosphate, enterotoxin, toxin
• Biological source: Clostridium difficile
• Total number of polymer chains: 2
• Total formula weight: 61743.91

Authors

Pruitt, R.N.,Lacy, D.B. (deposition date: 2009-06-01, release date: 2009-06-23, Last modification date: 2024-02-21)

Primary citation

Pruitt, R.N.,Chagot, B.,Cover, M.,Chazin, W.J.,Spiller, B.,Lacy, D.B.
Structure-function analysis of inositol hexakisphosphate-induced autoprocessing in Clostridium difficile toxin A.
J.Biol.Chem., 284:21934-21940, 2009

PubMed Abstract: 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.

PubMed: 19553670
DOI: 10.1074/jbc.M109.018929

Experimental method

X-RAY DIFFRACTION (1.6 Å)