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| | ==Structure of profragilysin-3 from Bacteroides fragilis== | | ==Structure of profragilysin-3 from Bacteroides fragilis== |
| - | <StructureSection load='3p24' size='340' side='right' caption='[[3p24]], [[Resolution|resolution]] 1.80Å' scene=''> | + | <StructureSection load='3p24' size='340' side='right'caption='[[3p24]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3p24]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacteroides_inaequalis"_eggerth_and_gagnon_1933 "bacteroides inaequalis" eggerth and gagnon 1933]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P24 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3P24 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3p24]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacteroides_fragilis Bacteroides fragilis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P24 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3P24 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AZI:AZIDE+ION'>AZI</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 1.8Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">bft-3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=817 "Bacteroides inaequalis" Eggerth and Gagnon 1933])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AZI:AZIDE+ION'>AZI</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Fragilysin Fragilysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.74 3.4.24.74] </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=3p24 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p24 OCA], [https://pdbe.org/3p24 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3p24 RCSB], [https://www.ebi.ac.uk/pdbsum/3p24 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3p24 ProSAT]</span></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=3p24 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p24 OCA], [http://pdbe.org/3p24 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3p24 RCSB], [http://www.ebi.ac.uk/pdbsum/3p24 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3p24 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/O86049_BACFG O86049_BACFG] |
| - | Enterotoxigenic Bacteroides fragilis is the most frequent disease-causing anaerobe in the intestinal tract of humans and livestock and its specific virulence factor is fragilysin, also known as B. fragilis toxin. This is a 21-kDa zinc-dependent metallopeptidase existing in three closely related isoforms that hydrolyze E-cadherin and contribute to secretory diarrhea, and possibly to inflammatory bowel disease and colorectal cancer. Here we studied the function and zymogenic structure of fragilysin-3 and found that its activity is repressed by a approximately 170-residue prodomain, which is the largest hitherto structurally characterized for a metallopeptidase. This prodomain plays a role in both the latency and folding stability of the catalytic domain and it has no significant sequence similarity to any known protein. The prodomain adopts a novel fold and inhibits the protease domain via an aspartate-switch mechanism. The catalytic fragilysin-3 moiety is active against several protein substrates and its structure reveals a new family prototype within the metzincin clan of metallopeptidases. It shows high structural similarity despite negligible sequence identity to adamalysins/ADAMs, which have only been described in eukaryotes. Because no similar protein has been found outside enterotoxigenic B. fragilis, our findings support that fragilysins derived from a mammalian adamalysin/ADAM xenolog that was co-opted by B. fragilis through a rare case of horizontal gene transfer from a eukaryotic cell to a bacterial cell. Subsequently, this co-opted peptidase was provided with a unique chaperone and latency maintainer in the time course of evolution to render a robust and dedicated toxin to compromise the intestinal epithelium of mammalian hosts.
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| - | Structure, function and latency regulation of a bacterial enterotoxin potentially derived from a mammalian adamalysin/ADAM xenolog.,Goulas T, Arolas JL, Gomis-Ruth FX Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):1856-61. Epub 2011 Jan 13. PMID:21233422<ref>PMID:21233422</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
| + | |
| - | <div class="pdbe-citations 3p24" style="background-color:#fffaf0;"></div>
| + | |
| - | == References ==
| + | |
| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacteroides inaequalis eggerth and gagnon 1933]] | + | [[Category: Bacteroides fragilis]] |
| - | [[Category: Fragilysin]] | + | [[Category: Large Structures]] |
| - | [[Category: Arolas, J L]] | + | [[Category: Arolas JL]] |
| - | [[Category: Gomis-Ruth, F X]] | + | [[Category: Gomis-Ruth FX]] |
| - | [[Category: Goulas, T]] | + | [[Category: Goulas T]] |
| - | [[Category: Hydrolase]]
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| - | [[Category: Metalloendopeptidase]]
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| - | [[Category: Metzincin]]
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