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| - | ==STRUCTURE OF KARILYSIN CATALYTIC MMP DOMAIN== | + | |
| - | <StructureSection load='2xs3' size='340' side='right' caption='[[2xs3]], [[Resolution|resolution]] 2.40Å' scene=''> | + | ==Structure of karilysin catalytic MMP domain== |
| | + | <StructureSection load='2xs3' size='340' side='right'caption='[[2xs3]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2xs3]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Tannerella_forsythia Tannerella forsythia] and [http://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XS3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XS3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2xs3]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Tannerella_forsythia Tannerella forsythia] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XS3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XS3 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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]] 2.4Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2xs4|2xs4]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=2xs3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xs3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2xs3 RCSB], [http://www.ebi.ac.uk/pdbsum/2xs3 PDBsum]</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=2xs3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xs3 OCA], [https://pdbe.org/2xs3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xs3 RCSB], [https://www.ebi.ac.uk/pdbsum/2xs3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xs3 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/KLY_TANFA KLY_TANFA] Metalloprotease able to cleave casein, gelatin, elastin, fibrinogen and fibronectin. Shows exclusive preference for hydrophobic residues, especially Leu, Tyr and Met, at the P1' position of substrates, and for Pro or Ala at P3. Can efficiently cleave the antimicrobial peptide LL-37 which is a component of the immune system, leading to a significant reduction of its bactericidal activity. Is also able to inhibit all pathways of the human complement system. The classical and lectin complement pathways are inhibited because of the efficient degradation of mannose-binding lectin, ficolin-2, ficolin-3, and C4 by karilysin, whereas inhibition of the terminal pathway is caused by cleavage of C5. Thus, karilysin appears to be a major virulence factor of T.forsythia that contributes to evasion of the human immune response and periodontal disease. Seems to act synergistically with gingipains from the periodontal pathogen P.gingivalis present at the same sites of infection.<ref>PMID:19919176</ref> <ref>PMID:20375548</ref> <ref>PMID:21166898</ref> <ref>PMID:22287711</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 2xs3" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Synthetic construct]] | | [[Category: Synthetic construct]] |
| | [[Category: Tannerella forsythia]] | | [[Category: Tannerella forsythia]] |
| - | [[Category: Arolas, J L.]] | + | [[Category: Arolas JL]] |
| - | [[Category: Cerda-Costa, N.]] | + | [[Category: Cerda-Costa N]] |
| - | [[Category: Gomis-Ruth, F X.]] | + | [[Category: Gomis-Ruth FX]] |
| - | [[Category: Guevara, T.]] | + | [[Category: Guevara T]] |
| - | [[Category: Karim, A Y.]] | + | [[Category: Karim AY]] |
| - | [[Category: Ksiazek, M.]] | + | [[Category: Ksiazek M]] |
| - | [[Category: Nguyen, K A.]] | + | [[Category: Nguyen K-A]] |
| - | [[Category: Potempa, J.]] | + | [[Category: Potempa J]] |
| - | [[Category: Bacterial mmp]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Metalloprotease]]
| + | |
| - | [[Category: Peptidase]]
| + | |
| - | [[Category: Virulence factor]]
| + | |
| - | [[Category: Zinc-dependent]]
| + | |
| Structural highlights
Function
KLY_TANFA Metalloprotease able to cleave casein, gelatin, elastin, fibrinogen and fibronectin. Shows exclusive preference for hydrophobic residues, especially Leu, Tyr and Met, at the P1' position of substrates, and for Pro or Ala at P3. Can efficiently cleave the antimicrobial peptide LL-37 which is a component of the immune system, leading to a significant reduction of its bactericidal activity. Is also able to inhibit all pathways of the human complement system. The classical and lectin complement pathways are inhibited because of the efficient degradation of mannose-binding lectin, ficolin-2, ficolin-3, and C4 by karilysin, whereas inhibition of the terminal pathway is caused by cleavage of C5. Thus, karilysin appears to be a major virulence factor of T.forsythia that contributes to evasion of the human immune response and periodontal disease. Seems to act synergistically with gingipains from the periodontal pathogen P.gingivalis present at the same sites of infection.[1] [2] [3] [4]
Publication Abstract from PubMed
Metallopeptidases (MPs) are among virulence factors secreted by pathogenic bacteria at the site of infection. One such pathogen is Tannerella forsythia, a member of the microbial consortium that causes peridontitis, arguably the most prevalent infective chronic inflammatory disease known to mankind. The only reported MP secreted by T. forsythia is karilysin, a 52 kDa multidomain protein comprising a central 18 kDa catalytic domain (CD), termed Kly18, flanked by domains unrelated to any known protein. We analysed the 3D structure of Kly18 in the absence and presence of Mg(2+) or Ca(2+) , which are required for function and stability, and found that it evidences most of the structural features characteristic of the CDs of mammalian matrix metalloproteinases (MMPs). Unexpectedly, a peptide was bound to the active-site cleft of Kly18 mimicking a left-behind cleavage product, which revealed that the specificity pocket accommodates bulky hydrophobic side-chains of substrates as in mammalian MMPs. In addition, Kly18 displayed a unique Mg(2+) or Ca(2+) binding site and two flexible segments that could play a role in substrate binding. Phylogenetic and sequence similarity studies revealed that Kly18 is evolutionarily much closer to winged-insect and mammalian MMPs than to potential bacterial counterparts found by genomic sequencing projects. Therefore, we conclude that this first structurally characterized non-mammalian MMP is a xenologue co-opted through horizontal gene transfer during the intimate coexistence between T. forsythia and humans or other animals, in a very rare case of gene shuffling from eukaryotes to prokaryotes. Subsequently, this protein would have evolved in a bacterial environment to give rise to full-length karilysin that is furnished with unique flanking domains that do not conform to the general multidomain architecture of animal MMPs.
The structure of the catalytic domain of Tannerella forsythia karilysin reveals it is a bacterial xenologue of animal matrix metalloproteinases.,Cerda-Costa N, Guevara T, Karim AY, Ksiazek M, Nguyen KA, Arolas JL, Potempa J, Gomis-Ruth FX Mol Microbiol. 2011 Jan;79(1):119-132. doi:, 10.1111/j.1365-2958.2010.07434.x. Epub 2010 Nov 2. PMID:21166898[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Karim AY, Kulczycka M, Kantyka T, Dubin G, Jabaiah A, Daugherty PS, Thogersen IB, Enghild JJ, Nguyen KA, Potempa J. A novel matrix metalloprotease-like enzyme (karilysin) of the periodontal pathogen Tannerella forsythia ATCC 43037. Biol Chem. 2010 Jan;391(1):105-17. PMID:19919176 doi:10.1515/BC.2010.009
- ↑ Koziel J, Karim AY, Przybyszewska K, Ksiazek M, Rapala-Kozik M, Nguyen KA, Potempa J. Proteolytic inactivation of LL-37 by karilysin, a novel virulence mechanism of Tannerella forsythia. J Innate Immun. 2010;2(3):288-93. Epub 2010 Feb 4. PMID:20375548 doi:10.1159/000281881
- ↑ Cerda-Costa N, Guevara T, Karim AY, Ksiazek M, Nguyen KA, Arolas JL, Potempa J, Gomis-Ruth FX. The structure of the catalytic domain of Tannerella forsythia karilysin reveals it is a bacterial xenologue of animal matrix metalloproteinases. Mol Microbiol. 2011 Jan;79(1):119-132. doi:, 10.1111/j.1365-2958.2010.07434.x. Epub 2010 Nov 2. PMID:21166898 doi:10.1111/j.1365-2958.2010.07434.x
- ↑ Jusko M, Potempa J, Karim AY, Ksiazek M, Riesbeck K, Garred P, Eick S, Blom AM. A metalloproteinase karilysin present in the majority of Tannerella forsythia isolates inhibits all pathways of the complement system. J Immunol. 2012 Mar 1;188(5):2338-49. doi: 10.4049/jimmunol.1101240. Epub 2012, Jan 27. PMID:22287711 doi:http://dx.doi.org/10.4049/jimmunol.1101240
- ↑ Cerda-Costa N, Guevara T, Karim AY, Ksiazek M, Nguyen KA, Arolas JL, Potempa J, Gomis-Ruth FX. The structure of the catalytic domain of Tannerella forsythia karilysin reveals it is a bacterial xenologue of animal matrix metalloproteinases. Mol Microbiol. 2011 Jan;79(1):119-132. doi:, 10.1111/j.1365-2958.2010.07434.x. Epub 2010 Nov 2. PMID:21166898 doi:10.1111/j.1365-2958.2010.07434.x
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