3pee

Structure of the C. difficile TcdB cysteine protease domain

spinqualitylabelsall models 3pee, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3pee is a 2 chain structure with sequence from Clostridioides difficile 630. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.1Å Ligands: CA, IHP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q189K3_CLOD6 Publication Abstract from PubMed An internal cysteine protease domain (CPD) autoproteolytically regulates Clostridium difficile glucosylating toxins by releasing a cytotoxic effector domain into target cells. CPD activity is itself allosterically regulated by the eukaryote-specific molecule inositol hexakisphosphate (InsP(6)). Although allostery controls the function of most proteins, the molecular details underlying this regulatory mechanism are often difficult to characterize. Here we use chemical probes to show that apo-CPD is in dynamic equilibrium between active and inactive states. InsP(6) markedly shifts this equilibrium toward an active conformer that is further restrained upon binding a suicide substrate. Structural analyses combined with systematic mutational and disulfide bond engineering studies show that residues within a beta-hairpin region functionally couple the InsP(6)-binding site to the active site. Collectively, our results identify an allosteric circuit that allows bacterial virulence factors to sense and respond to the eukaryotic environment. Defining an allosteric circuit in the cysteine protease domain of Clostridium difficile toxins.,Shen A, Lupardus PJ, Gersch MM, Puri AW, Albrow VE, Garcia KC, Bogyo M Nat Struct Mol Biol. 2011 Mar;18(3):364-71. Epub 2011 Feb 13. PMID:21317893 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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