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| | <StructureSection load='6uwi' size='340' side='right'caption='[[6uwi]], [[Resolution|resolution]] 3.70Å' scene=''> | | <StructureSection load='6uwi' size='340' side='right'caption='[[6uwi]], [[Resolution|resolution]] 3.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6uwi]] is a 28 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UWI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UWI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6uwi]] is a 28 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridioides_difficile Clostridioides difficile]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UWI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UWI FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</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]] 3.7Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6uwi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uwi OCA], [http://pdbe.org/6uwi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6uwi RCSB], [http://www.ebi.ac.uk/pdbsum/6uwi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6uwi ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</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=6uwi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uwi OCA], [https://pdbe.org/6uwi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uwi RCSB], [https://www.ebi.ac.uk/pdbsum/6uwi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uwi ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/O32739_CLODI O32739_CLODI] |
| - | Targeting Clostridium difficile infection is challenging because treatment options are limited, and high recurrence rates are common. One reason for this is that hypervirulent C. difficile strains often have a binary toxin termed the C. difficile toxin, in addition to the enterotoxins TsdA and TsdB. The C. difficile toxin has an enzymatic component, termed CDTa, and a pore-forming or delivery subunit termed CDTb. CDTb was characterized here using a combination of single-particle cryoelectron microscopy, X-ray crystallography, NMR, and other biophysical methods. In the absence of CDTa, 2 di-heptamer structures for activated CDTb (1.0 MDa) were solved at atomic resolution, including a symmetric ((Sym)CDTb; 3.14 A) and an asymmetric form ((Asym)CDTb; 2.84 A). Roles played by 2 receptor-binding domains of activated CDTb were of particular interest since the receptor-binding domain 1 lacks sequence homology to any other known toxin, and the receptor-binding domain 2 is completely absent in other well-studied heptameric toxins (i.e., anthrax). For (Asym)CDTb, a Ca(2+) binding site was discovered in the first receptor-binding domain that is important for its stability, and the second receptor-binding domain was found to be critical for host cell toxicity and the di-heptamer fold for both forms of activated CDTb. Together, these studies represent a starting point for developing structure-based drug-design strategies to target the most severe strains of C. difficile.
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| - | | + | |
| - | Structure of the cell-binding component of the Clostridium difficile binary toxin reveals a di-heptamer macromolecular assembly.,Xu X, Godoy-Ruiz R, Adipietro KA, Peralta C, Ben-Hail D, Varney KM, Cook ME, Roth BM, Wilder PT, Cleveland T, Grishaev A, Neu HM, Michel SLJ, Yu W, Beckett D, Rustandi RR, Lancaster C, Loughney JW, Kristopeit A, Christanti S, Olson JW, MacKerell AD, Georges AD, Pozharski E, Weber DJ Proc Natl Acad Sci U S A. 2020 Jan 14;117(2):1049-1058. doi:, 10.1073/pnas.1919490117. Epub 2020 Jan 2. PMID:31896582<ref>PMID:31896582</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6uwi" style="background-color:#fffaf0;"></div>
| + | |
| - | == References ==
| + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Clostridioides difficile]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Pozharski, E]] | + | [[Category: Pozharski E]] |
| - | [[Category: Toxin]]
| + | |
| - | [[Category: Translocase]]
| + | |
