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| <StructureSection load='2quo' size='340' side='right'caption='[[2quo]], [[Resolution|resolution]] 1.75Å' scene=''> | | <StructureSection load='2quo' size='340' side='right'caption='[[2quo]], [[Resolution|resolution]] 1.75Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[2quo]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_perfringens"_veillon_and_zuber_1898 "bacillus perfringens" veillon and zuber 1898]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QUO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QUO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2quo]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_perfringens Clostridium perfringens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QUO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QUO FirstGlance]. <br> |
- | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.75Å</td></tr> |
- | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CPE ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1502 "Bacillus perfringens" Veillon and Zuber 1898])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2quo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2quo OCA], [https://pdbe.org/2quo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2quo RCSB], [https://www.ebi.ac.uk/pdbsum/2quo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2quo ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2quo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2quo OCA], [https://pdbe.org/2quo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2quo RCSB], [https://www.ebi.ac.uk/pdbsum/2quo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2quo ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function == | | == Function == |
- | [[https://www.uniprot.org/uniprot/ELTB_CLOPF ELTB_CLOPF]] This enterotoxin is responsible for many cases of a mild type of food poisoning.
| + | [https://www.uniprot.org/uniprot/ELTB_CLOPF ELTB_CLOPF] This enterotoxin is responsible for many cases of a mild type of food poisoning. |
- | <div style="background-color:#fffaf0;">
| + | |
- | == 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<ref>PMID:17977833</ref>
| + | |
- | | + | |
- | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
- | </div>
| + | |
- | <div class="pdbe-citations 2quo" style="background-color:#fffaf0;"></div>
| + | |
- | == References ==
| + | |
- | <references/>
| + | |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
- | [[Category: Bacillus perfringens veillon and zuber 1898]] | + | [[Category: Clostridium perfringens]] |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
- | [[Category: Betts, L]] | + | [[Category: Betts L]] |
- | [[Category: Itallie, C M.Van]] | + | [[Category: Van Itallie CM]] |
- | [[Category: Beta sandwich]]
| + | |
- | [[Category: Claudin-4 binding domain]]
| + | |
- | [[Category: Enterotoxin]]
| + | |
- | [[Category: Therapeutic agent]]
| + | |
- | [[Category: Toxin]]
| + | |