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4r3v

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Revision as of 17:15, 18 January 2017

Structure of karilysin propeptide and catalytic MMP domain

Structural highlights

4r3v is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	2xs3, 2xs4, 4in9
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

The matrix metalloproteinases (MMPs) are a family of secreted soluble or membrane-anchored multi-modular peptidases regularly found in several paralogous copies in animals and plants, where they have multiple functions. The minimal consensus domain architecture comprises a signal peptide, a 60-to-90-residue globular pro-domain with a conserved sequence motif including a cysteine engaged in cysteine-switch or Velcro mediated latency, and a catalytic domain. Karilysin, from the human periodontopathogen Tannerella forsythia, is the only bacterial MMP to have been characterized biochemically to date. It shares with eukaryotic forms the catalytic domain but none of the flanking domains. Instead of the consensus MMP pro-domain, it features a 14-residue pro-peptide, the shortest reported for a metallopeptidase, which lacks cysteines. Here we determined the structure of a pro-karilysin fragment encompassing the pro-peptide and the catalytic domain, and found that the former runs across the cleft in the opposite direction to a bound substrate and inhibits the latter through an aspartate-switch mechanism. This finding is reminiscent of latency maintenance in the otherwise unrelated astacin and fragilysin metallopeptidase families. In addition, in vivo and biochemical assays showed that the pro-peptide contributes to protein folding and stability. Our analysis of pro-karilysin reveals a novel mechanism of latency and activation in MMPs. Finally, our findings support the view that the karilysin catalytic domain was co-opted by competent bacteria through horizontal gene transfer from a eukaryotic source, and later evolved in a specific bacterial environment.

A novel mechanism of latency in matrix metalloproteinases.,L Oacutepez-Pelegrin M, Ksiazek M, Karim AY, Guevara T, Arolas JL, Potempa J, Gomis-R Uumlth FX J Biol Chem. 2015 Jan 2. pii: jbc.M114.605956. PMID:25555916^[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
↑ L Oacutepez-Pelegrin M, Ksiazek M, Karim AY, Guevara T, Arolas JL, Potempa J, Gomis-R Uumlth FX. A novel mechanism of latency in matrix metalloproteinases. J Biol Chem. 2015 Jan 2. pii: jbc.M114.605956. PMID:25555916 doi:http://dx.doi.org/10.1074/jbc.M114.605956

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4r3v"

@@ Line 1: / Line 1: @@
 ==Structure of karilysin propeptide and catalytic MMP domain==
 <StructureSection load='4r3v' size='340' side='right' caption='[[4r3v]], [[Resolution|resolution]] 2.01&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2xs3|2xs3]], [[2xs4|2xs4]], [[4in9|4in9]]</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=4r3v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r3v OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4r3v RCSB], [http://www.ebi.ac.uk/pdbsum/4r3v PDBsum]</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=4r3v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r3v OCA], [http://pdbe.org/4r3v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4r3v RCSB], [http://www.ebi.ac.uk/pdbsum/4r3v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4r3v ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4r3v" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4r3v

From Proteopedia

Revision as of 17:15, 18 January 2017

Structure of karilysin propeptide and catalytic MMP domain

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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