| IED ID | IndEnz0002005784 |
| Enzyme Type ID | protease005784 |
| Protein Name |
Karilysin EC 3.4.24.- Matrix metalloprotease-like enzyme MMP-like enzyme Cleaved into: Karilysin long form Kly38; Karilysin short form Kly18 |
| Gene Name | kly BFO_2683 |
| Organism | Tannerella forsythia (strain ATCC 43037 / JCM 10827 / CCUG 33226 / KCTC 5666 / FDC 338) (Bacteroides forsythus) |
| Taxonomic Lineage | cellular organisms Bacteria FCB group Bacteroidetes/Chlorobi group Bacteroidetes Bacteroidia Bacteroidales Tannerellaceae Tannerella Tannerella forsythia (Bacteroides forsythus) Tannerella forsythia (strain ATCC 43037 / JCM 10827 / CCUG 33226 / KCTC 5666 / FDC 338) (Bacteroides forsythus) |
| Enzyme Sequence | MKRFILLFFLSTIAIFKVYSQRLYDNGPLTGDNNYVLQGSKWNKTTLKYYIYNSSSHLTTTERENAIRSAFALWSDKSTLSFIQVYNPNQADIKIKWEKGNHGDGYPFDGNTGILAHAFYPPPAGGNYAGHLHFDGDENWSINGSGIDLITVAAHEIGHLLGIEHSNVSSALMYPYYTGIKRQLDNDDCLAVWDLYGYPFSISGPSSVCDQATYTVENLLSGATVQWSVSNPNIATINSSNGVLTCRGNGICEVRATINNSSVALTPLKICLGTPISQDITLTVESLNSNGTLCTDNPNAIMADHPGGNHLGYIREYEWRISNGWQIAHHPGDNGIYADHFIVTVIPLSPLPGSPTVSVRARSECGWGTWKEVQIPAVSCSRTISPFTLSPNPATDEVILQLMETDEVSGLSVLSTDRSAYEIQIWSGMRMLRSFRTNEPTFQISMTGLPAGLYFVRVVKNGQTYTQKLIKK |
| Enzyme Length | 472 |
| Uniprot Accession Number | D0EM77 |
| Absorption | |
| Active Site | ACT_SITE 156; /note="Proton donor/acceptor"; /evidence="ECO:0000255|PROSITE-ProRule:PRU10095, ECO:0000269|PubMed:21166898, ECO:0000269|PubMed:23695557" |
| Activity Regulation | ACTIVITY REGULATION: 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). {ECO:0000269|PubMed:19919176, ECO:0000269|PubMed:23119051}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | 3.4.24.- |
| Enzyme Function | FUNCTION: 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. {ECO:0000269|PubMed:19919176, ECO:0000269|PubMed:20375548, ECO:0000269|PubMed:21166898, ECO:0000269|PubMed:22287711}. |
| Temperature Dependency | BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: 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. {ECO:0000269|PubMed:19919176}; |
| PH Dependency | BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 8 for casein degradation. Active in the broad pH range from 6.5 to 8.5. {ECO:0000269|PubMed:19919176}; |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (1); Beta strand (10); Chain (2); Frameshift (1); Helix (5); Metal binding (7); Mutagenesis (2); Propeptide (3); Sequence caution (1); Sequence conflict (17); Signal peptide (1); Turn (2) |
| Keywords | 3D-structure;Autocatalytic cleavage;Direct protein sequencing;Hydrolase;Metal-binding;Metalloprotease;Protease;Reference proteome;Secreted;Signal;Virulence;Zinc;Zymogen |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Secreted {ECO:0000305}. |
| Modified Residue | |
| Post Translational Modification | PTM: 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. |
| Signal Peptide | SIGNAL 1..20; /evidence=ECO:0000255 |
| Structure 3D | X-ray crystallography (4) |
| Cross Reference PDB | 2XS3; 2XS4; 4IN9; 4R3V; |
| Mapped Pubmed ID | 25555916; |
| Motif | |
| Gene Encoded By | |
| Mass | 52,061 |
| Kinetics | |
| Metal Binding | METAL 102; /note="Zinc 1; via tele nitrogen"; /evidence="ECO:0000269|PubMed:21166898, ECO:0000269|PubMed:23695557"; METAL 104; /note="Zinc 1"; /evidence="ECO:0000269|PubMed:21166898, ECO:0000269|PubMed:23695557"; METAL 117; /note="Zinc 1; via tele nitrogen"; /evidence="ECO:0000269|PubMed:21166898, ECO:0000269|PubMed:23695557"; METAL 133; /note="Zinc 1; via pros nitrogen"; /evidence="ECO:0000269|PubMed:21166898, ECO:0000269|PubMed:23695557"; METAL 155; /note="Zinc 2; via tele nitrogen; catalytic"; /evidence="ECO:0000269|PubMed:21166898, ECO:0000269|PubMed:23695557"; METAL 159; /note="Zinc 2; via tele nitrogen; catalytic"; /evidence="ECO:0000269|PubMed:21166898, ECO:0000269|PubMed:23695557"; METAL 165; /note="Zinc 2; via tele nitrogen; catalytic"; /evidence="ECO:0000269|PubMed:21166898, ECO:0000269|PubMed:23695557" |
| Rhea ID | |
| Cross Reference Brenda |