3pa8
From Proteopedia
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| - | + | ==Structure of the C. difficile TcdB cysteine protease domain in complex with a peptide inhibitor== | |
| - | + | <StructureSection load='3pa8' size='340' side='right' caption='[[3pa8]], [[Resolution|resolution]] 2.00Å' scene=''> | |
| - | + | == Structural highlights == | |
| + | <table><tr><td colspan='2'>[[3pa8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Clostridium_difficile_630 Clostridium difficile 630]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PA8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3PA8 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=621:N-ACETYLGLYCYL-N-[(3S)-1-HYDROXY-5-METHYL-2-OXOHEXAN-3-YL]-L-SERINAMIDE'>621</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=IHP:INOSITOL+HEXAKISPHOSPHATE'>IHP</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CD0660, tcdB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=272563 Clostridium difficile 630])</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=3pa8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pa8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3pa8 RCSB], [http://www.ebi.ac.uk/pdbsum/3pa8 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Clostridium difficile is a leading cause of nosocomial infections. The major virulence factors of this pathogen are the multi-domain toxins TcdA and TcdB. These toxins contain a cysteine protease domain (CPD) that autoproteolytically releases a cytotoxic effector domain upon binding intracellular inositol hexakisphosphate. Currently, there are no known inhibitors of this protease. Here, we describe the rational design of covalent small molecule inhibitors of TcdB CPD. We identified compounds that inactivate TcdB holotoxin function in cells and solved the structure of inhibitor-bound protease to 2.0 A. This structure reveals the molecular basis of CPD substrate recognition and informed the synthesis of activity-based probes for this enzyme. The inhibitors presented will guide the development of therapeutics targeting C. difficile, and the probes will serve as tools for studying the unique activation mechanism of bacterial toxin CPDs. | ||
| - | + | Rational design of inhibitors and activity-based probes targeting Clostridium difficile virulence factor TcdB.,Puri AW, Lupardus PJ, Deu E, Albrow VE, Garcia KC, Bogyo M, Shen A Chem Biol. 2010 Nov 24;17(11):1201-11. PMID:21095570<ref>PMID:21095570</ref> | |
| - | + | ||
| - | == | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | + | </div> | |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Clostridium difficile 630]] | [[Category: Clostridium difficile 630]] | ||
| - | [[Category: Garcia, K C | + | [[Category: Garcia, K C]] |
| - | [[Category: Lupardus, P J | + | [[Category: Lupardus, P J]] |
[[Category: Clan cd cysteine protease]] | [[Category: Clan cd cysteine protease]] | ||
[[Category: Protease]] | [[Category: Protease]] | ||
[[Category: Toxin]] | [[Category: Toxin]] | ||
[[Category: Toxin-peptide inhibitor complex]] | [[Category: Toxin-peptide inhibitor complex]] | ||
Revision as of 06:52, 19 December 2014
Structure of the C. difficile TcdB cysteine protease domain in complex with a peptide inhibitor
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