4r3v

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]}

References

1. ↑ 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
2. ↑ 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
3. ↑ 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
4. ↑ 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