2quo | pdb_00002quo

Crystal Structure of C terminal fragment of Clostridium perfringens enterotoxin

spinqualitylabelsall models 2quo, resolution 1.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2quo is a 1 chain structure with sequence from "bacillus_perfringens"_veillon_and_zuber_1898 "bacillus perfringens" veillon and zuber 1898. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: SO4 Gene: CPE ("Bacillus perfringens" Veillon and Zuber 1898) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ELTB_CLOPF] This enterotoxin is responsible for many cases of a mild type of food poisoning. Publication Abstract from PubMed Clostridium perfringens enterotoxin is a common cause of food-borne and antibiotic-associated diarrhea. The toxin's receptors on intestinal epithelial cells include claudin-3 and -4, members of a large family of tight junction proteins. Toxin-induced cytolytic pore formation requires residues in the NH(2)-terminal half, whereas residues near the COOH terminus are required for binding to claudins. The claudin-binding COOH-terminal domain is not toxic and is currently under investigation as a potential drug absorption enhancer. Because claudin-4 is overexpressed on some human cancers, the toxin is also being investigated for targeting chemotherapy. Our aim was to solve the structure of the claudin-binding domain to advance its therapeutic applications. The structure of a 14-kDa fragment containing residues 194 to the native COOH terminus at position 319 was solved by x-ray diffraction to a resolution of 1.75A. The structure is a nine-strand beta sandwich with previously unappreciated similarity to the receptor-binding domains of several other toxins of spore-forming bacteria, including the collagen-binding domain of ColG from Clostridium histolyticum and the large Cry family of toxins (including Cry4Ba) of Bacillus thuringiensis. Correlations with previous studies suggest that the claudin-4 binding site is on a large surface loop between strands beta8 and beta9 or includes these strands. The sequence that was crystallized (residues 194-319) binds to purified human claudin-4 with a 1:1 stoichiometry and affinity in the submicromolar range similar to that observed for binding of native toxin to cells. Our results provide a structural framework to advance therapeutic applications of the toxin and suggest a common ancestor for several receptor-binding domains of bacterial toxins. Structure of the claudin-binding domain of Clostridium perfringens enterotoxin.,Van Itallie CM, Betts L, Smedley JG 3rd, McClane BA, Anderson JM J Biol Chem. 2008 Jan 4;283(1):268-74. Epub 2007 Oct 31. PMID:17977833 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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