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. Binds 2 Zn(2+) ions per subunit. Autoprocessing and proteolytic activity are completely inhibited by EDTA and 1,10-phenanthroline in vitro. Proteolytic activity is 3-fold enhanced by Ca(2+) due to stabilization of the protein structure but inhibited by an excess of Zn(2+) (PubMed:19919176). Inhibitory studies of karilysin identified several phage display-selected peptides with apparent inhibition constants (Ki) in the micromolar range, among which is the tetrapeptide SWFP (Ki=10.7 uM) (PubMed:23119051). Optimum pH is 8 for casein degradation. Active in the broad pH range from 6.5 to 8.5. In the presence of CaCl(2), the enzyme is fully stable for up to 40 minutes at 70 degrees Celsius, whereas karilysin incubated without calcium loses 50% of its activity within 30 minutes. Processes itself into the mature 18-kDa enzyme (Kly18) through sequential autoproteolytic cleavage at both the N- and C-termini. However, the maturation intermediate Kly38 is found to be more active than Kly18 and the rate for its processing is slow, which raises the question as to whether Kly38 is a physiologically relevant entity. Belongs to the peptidase M10A family. Sequence submitted to GenBank under accession ACW82491.1 does not completely correspond to the one described in the related article, which is the correct one. Region of major discrepancy (238-386) presumably comes from incorrect genome shotgun sequence assembly of homologous regions with other proteases.