KLY_TANFA
ID KLY_TANFA Reviewed; 472 AA.
AC D0EM77;
DT 19-MAR-2014, integrated into UniProtKB/Swiss-Prot.
DT 19-MAR-2014, sequence version 2.
DT 03-AUG-2022, entry version 57.
DE RecName: Full=Karilysin;
DE EC=3.4.24.-;
DE AltName: Full=Matrix metalloprotease-like enzyme;
DE Short=MMP-like enzyme;
DE Contains:
DE RecName: Full=Karilysin long form Kly38;
DE Contains:
DE RecName: Full=Karilysin short form Kly18;
DE Flags: Precursor;
GN Name=kly; OrderedLocusNames=BFO_2683;
OS Tannerella forsythia (strain ATCC 43037 / JCM 10827 / CCUG 21028 A / KCTC
OS 5666 / FDC 338) (Bacteroides forsythus).
OC Bacteria; Bacteroidetes; Bacteroidia; Bacteroidales; Tannerellaceae;
OC Tannerella.
OX NCBI_TaxID=203275;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], SEQUENCE REVISION, PARTIAL PROTEIN
RP SEQUENCE, FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, ACTIVITY
RP REGULATION, IDENTIFICATION BY MASS SPECTROMETRY, AUTOCATALYTIC CLEAVAGE,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF TYR-35 AND GLU-156.
RC STRAIN=ATCC 43037 / JCM 10827 / CCUG 21028 A / KCTC 5666 / FDC 338;
RX PubMed=19919176; DOI=10.1515/bc.2010.009;
RA Karim A.Y., Kulczycka M., Kantyka T., Dubin G., Jabaiah A., Daugherty P.S.,
RA Thogersen I.B., Enghild J.J., Nguyen K.A., Potempa J.;
RT "A novel matrix metalloprotease-like enzyme (karilysin) of the periodontal
RT pathogen Tannerella forsythia ATCC 43037.";
RL Biol. Chem. 391:105-117(2010).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 43037 / JCM 10827 / CCUG 21028 A / KCTC 5666 / FDC 338;
RA Dewhirst F., Tanner A., Izard J., Brinkac L., Durkin A.S., Hostetler J.,
RA Shetty J., Torralba M., Gill S., Nelson K.;
RT "Complete sequence of Tannerella forsythia ATCC 43037.";
RL Submitted (DEC-2011) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION.
RC STRAIN=ATCC 43037 / JCM 10827 / CCUG 21028 A / KCTC 5666 / FDC 338;
RX PubMed=20375548; DOI=10.1159/000281881;
RA Koziel J., Karim A.Y., Przybyszewska K., Ksiazek M., Rapala-Kozik M.,
RA Nguyen K.A., Potempa J.;
RT "Proteolytic inactivation of LL-37 by karilysin, a novel virulence
RT mechanism of Tannerella forsythia.";
RL J. Innate Immun. 2:288-293(2010).
RN [4]
RP FUNCTION, GENE NAME, AND MUTAGENESIS OF GLU-156.
RC STRAIN=ATCC 43037 / JCM 10827 / CCUG 21028 A / KCTC 5666 / FDC 338;
RX PubMed=22287711; DOI=10.4049/jimmunol.1101240;
RA Jusko M., Potempa J., Karim A.Y., Ksiazek M., Riesbeck K., Garred P.,
RA Eick S., Blom A.M.;
RT "A metalloproteinase karilysin present in the majority of Tannerella
RT forsythia isolates inhibits all pathways of the complement system.";
RL J. Immunol. 188:2338-2349(2012).
RN [5]
RP ACTIVITY REGULATION, AND INHIBITOR STUDIES.
RC STRAIN=ATCC 43037 / JCM 10827 / CCUG 21028 A / KCTC 5666 / FDC 338;
RX PubMed=23119051; DOI=10.1371/journal.pone.0048537;
RA Skottrup P.D., Sorensen G., Ksiazek M., Potempa J., Riise E.;
RT "A phage display selected 7-mer peptide inhibitor of the Tannerella
RT forsythia metalloprotease-like enzyme Karilysin can be truncated to Ser-
RT Trp-Phe-Pro.";
RL PLoS ONE 7:E48537-E48537(2012).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 35-201 IN COMPLEX WITH ZINC AND A
RP TRIPEPTIDE, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND ACTIVE SITE.
RC STRAIN=ATCC 43037 / JCM 10827 / CCUG 21028 A / KCTC 5666 / FDC 338;
RX PubMed=21166898; DOI=10.1111/j.1365-2958.2010.07434.x;
RA Cerda-Costa N., Guevara T., Karim A.Y., Ksiazek M., Nguyen K.A.,
RA Arolas J.L., Potempa J., Gomis-Ruth F.X.;
RT "The structure of the catalytic domain of Tannerella forsythia karilysin
RT reveals it is a bacterial xenologue of animal matrix metalloproteinases.";
RL Mol. Microbiol. 79:119-132(2011).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 35-200 IN COMPLEX WITH ZINC AND A
RP TETRAPEPTIDIC INHIBITOR, COFACTOR, AND ACTIVE SITE.
RC STRAIN=ATCC 43037 / JCM 10827 / CCUG 21028 A / KCTC 5666 / FDC 338;
RX PubMed=23695557; DOI=10.1107/s1744309113007392;
RA Guevara T., Ksiazek M., Skottrup P.D., Cerda-Costa N., Trillo-Muyo S.,
RA de Diego I., Riise E., Potempa J., Gomis-Ruth F.X.;
RT "Structure of the catalytic domain of the Tannerella forsythia matrix
RT metallopeptidase karilysin in complex with a tetrapeptidic inhibitor.";
RL Acta Crystallogr. F 69:472-476(2013).
CC -!- FUNCTION: Metalloprotease able to cleave casein, gelatin, elastin,
CC fibrinogen and fibronectin. Shows exclusive preference for hydrophobic
CC residues, especially Leu, Tyr and Met, at the P1' position of
CC substrates, and for Pro or Ala at P3. Can efficiently cleave the
CC antimicrobial peptide LL-37 which is a component of the immune system,
CC leading to a significant reduction of its bactericidal activity. Is
CC also able to inhibit all pathways of the human complement system. The
CC classical and lectin complement pathways are inhibited because of the
CC efficient degradation of mannose-binding lectin, ficolin-2, ficolin-3,
CC and C4 by karilysin, whereas inhibition of the terminal pathway is
CC caused by cleavage of C5. Thus, karilysin appears to be a major
CC virulence factor of T.forsythia that contributes to evasion of the
CC human immune response and periodontal disease. Seems to act
CC synergistically with gingipains from the periodontal pathogen
CC P.gingivalis present at the same sites of infection.
CC {ECO:0000269|PubMed:19919176, ECO:0000269|PubMed:20375548,
CC ECO:0000269|PubMed:21166898, ECO:0000269|PubMed:22287711}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:21166898, ECO:0000269|PubMed:23695557};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000269|PubMed:21166898,
CC ECO:0000269|PubMed:23695557};
CC -!- ACTIVITY REGULATION: Autoprocessing and proteolytic activity are
CC completely inhibited by EDTA and 1,10-phenanthroline in vitro.
CC Proteolytic activity is 3-fold enhanced by Ca(2+) due to stabilization
CC of the protein structure but inhibited by an excess of Zn(2+)
CC (PubMed:19919176). Inhibitory studies of karilysin identified several
CC phage display-selected peptides with apparent inhibition constants (Ki)
CC in the micromolar range, among which is the tetrapeptide SWFP (Ki=10.7
CC uM) (PubMed:23119051). {ECO:0000269|PubMed:19919176,
CC ECO:0000269|PubMed:23119051}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 8 for casein degradation. Active in the broad pH range
CC from 6.5 to 8.5. {ECO:0000269|PubMed:19919176};
CC Temperature dependence:
CC In the presence of CaCl(2), the enzyme is fully stable for up to 40
CC minutes at 70 degrees Celsius, whereas karilysin incubated without
CC calcium loses 50% of its activity within 30 minutes.
CC {ECO:0000269|PubMed:19919176};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC -!- PTM: Processes itself into the mature 18-kDa enzyme (Kly18) through
CC sequential autoproteolytic cleavage at both the N- and C-termini.
CC However, the maturation intermediate Kly38 is found to be more active
CC than Kly18 and the rate for its processing is slow, which raises the
CC question as to whether Kly38 is a physiologically relevant entity.
CC -!- SIMILARITY: Belongs to the peptidase M10A family. {ECO:0000305}.
CC -!- CAUTION: Sequence submitted to GenBank under accession ACW82491.1 does
CC not completely correspond to the one described in the related article,
CC which is the correct one. {ECO:0000305|PubMed:19919176}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CP003191; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CP003191; Type=Miscellaneous discrepancy; Note=Region of major discrepancy (238-386) presumably comes from incorrect genome shotgun sequence assembly of homologous regions with other proteases.; Evidence={ECO:0000305};
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DR EMBL; GQ856797; ACW82491.1; -; Genomic_DNA.
DR EMBL; CP003191; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PDB; 2XS3; X-ray; 2.40 A; A/B=35-200.
DR PDB; 2XS4; X-ray; 1.70 A; A=35-201.
DR PDB; 4IN9; X-ray; 1.55 A; A=35-200.
DR PDB; 4R3V; X-ray; 2.01 A; A/B=21-201.
DR PDBsum; 2XS3; -.
DR PDBsum; 2XS4; -.
DR PDBsum; 4IN9; -.
DR PDBsum; 4R3V; -.
DR AlphaFoldDB; D0EM77; -.
DR SMR; D0EM77; -.
DR MEROPS; M10.066; -.
DR TCDB; 8.B.14.2.4; the sea anemone peptide toxin, class 1 (bgk) family.
DR eggNOG; COG0265; Bacteria.
DR eggNOG; COG5549; Bacteria.
DR EvolutionaryTrace; D0EM77; -.
DR Proteomes; UP000005436; Chromosome.
DR GO; GO:0031012; C:extracellular matrix; IEA:InterPro.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd04278; ZnMc_MMP; 1.
DR Gene3D; 3.40.390.10; -; 1.
DR InterPro; IPR008964; Invasin/intimin_cell_adhesion.
DR InterPro; IPR033739; M10A_MMP.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR001818; Pept_M10_metallopeptidase.
DR InterPro; IPR021190; Pept_M10A.
DR InterPro; IPR006026; Peptidase_Metallo.
DR InterPro; IPR026444; Secre_tail.
DR Pfam; PF00413; Peptidase_M10; 1.
DR Pfam; PF18962; Por_Secre_tail; 1.
DR PRINTS; PR00138; MATRIXIN.
DR SMART; SM00235; ZnMc; 1.
DR SUPFAM; SSF49373; SSF49373; 1.
DR TIGRFAMs; TIGR04183; Por_Secre_tail; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Autocatalytic cleavage; Direct protein sequencing; Hydrolase;
KW Metal-binding; Metalloprotease; Protease; Reference proteome; Secreted;
KW Signal; Virulence; Zinc; Zymogen.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..34
FT /note="Activation peptide"
FT /id="PRO_0000425866"
FT CHAIN 35..386
FT /note="Karilysin long form Kly38"
FT /id="PRO_0000425867"
FT CHAIN 35..195
FT /note="Karilysin short form Kly18"
FT /id="PRO_0000425868"
FT PROPEP 196..386
FT /note="Removed in short form"
FT /id="PRO_0000425869"
FT PROPEP 387..472
FT /note="Removed in long form"
FT /id="PRO_0000425870"
FT ACT_SITE 156
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095,
FT ECO:0000269|PubMed:21166898, ECO:0000269|PubMed:23695557"
FT BINDING 102
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:21166898,
FT ECO:0000269|PubMed:23695557"
FT BINDING 104
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:21166898,
FT ECO:0000269|PubMed:23695557"
FT BINDING 117
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:21166898,
FT ECO:0000269|PubMed:23695557"
FT BINDING 133
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:21166898,
FT ECO:0000269|PubMed:23695557"
FT BINDING 155
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:21166898,
FT ECO:0000269|PubMed:23695557"
FT BINDING 159
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:21166898,
FT ECO:0000269|PubMed:23695557"
FT BINDING 165
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:21166898,
FT ECO:0000269|PubMed:23695557"
FT MUTAGEN 35
FT /note="Y->A: Hinders generation of active enzyme and
FT maturation process."
FT /evidence="ECO:0000269|PubMed:19919176"
FT MUTAGEN 156
FT /note="E->A: Fails to autocatalytically process, to destroy
FT the bactericidal activity of human serum and to inhibit all
FT the complement pathways."
FT /evidence="ECO:0000269|PubMed:19919176,
FT ECO:0000269|PubMed:22287711"
FT CONFLICT 136
FT /note="G -> D (in Ref. 1; ACW82491 and 2; CP003191)"
FT /evidence="ECO:0000305"
FT CONFLICT 220..221
FT /note="LS -> PA (in Ref. 2; CP003191)"
FT /evidence="ECO:0000305"
FT CONFLICT 224..226
FT /note="TVQ -> IVE (in Ref. 2; CP003191)"
FT /evidence="ECO:0000305"
FT CONFLICT 234
FT /note="I -> V (in Ref. 2; CP003191)"
FT /evidence="ECO:0000305"
FT CONFLICT 397..399
FT /note="EVI -> AVT (in Ref. 2; CP003191)"
FT /evidence="ECO:0000305"
FT CONFLICT 403
FT /note="M -> T (in Ref. 2; CP003191)"
FT /evidence="ECO:0000305"
FT CONFLICT 419..420
FT /note="SA -> TP (in Ref. 2; CP003191)"
FT /evidence="ECO:0000305"
FT CONFLICT 425
FT /note="I -> L (in Ref. 1; ACW82491)"
FT /evidence="ECO:0000305"
FT CONFLICT 430
FT /note="R -> T (in Ref. 1; ACW82491 and 2; CP003191)"
FT /evidence="ECO:0000305"
FT CONFLICT 438
FT /note="N -> D (in Ref. 1; ACW82491)"
FT /evidence="ECO:0000305"
FT CONFLICT 443
FT /note="Q -> S (in Ref. 2; CP003191)"
FT /evidence="ECO:0000305"
FT CONFLICT 445..447
FT /note="SMT -> PMA (in Ref. 1; ACW82491 and 2; CP003191)"
FT /evidence="ECO:0000305"
FT CONFLICT 461
FT /note="N -> D (in Ref. 1; ACW82491 and 2; CP003191)"
FT /evidence="ECO:0000305"
FT TURN 33..35
FT /evidence="ECO:0007829|PDB:4R3V"
FT STRAND 43..51
FT /evidence="ECO:0007829|PDB:4IN9"
FT STRAND 56..58
FT /evidence="ECO:0007829|PDB:4R3V"
FT HELIX 60..76
FT /evidence="ECO:0007829|PDB:4IN9"
FT STRAND 81..84
FT /evidence="ECO:0007829|PDB:4IN9"
FT HELIX 88..90
FT /evidence="ECO:0007829|PDB:4IN9"
FT STRAND 92..98
FT /evidence="ECO:0007829|PDB:4IN9"
FT STRAND 103..105
FT /evidence="ECO:0007829|PDB:4IN9"
FT STRAND 108..113
FT /evidence="ECO:0007829|PDB:4IN9"
FT STRAND 115..118
FT /evidence="ECO:0007829|PDB:4IN9"
FT TURN 121..125
FT /evidence="ECO:0007829|PDB:4IN9"
FT HELIX 126..128
FT /evidence="ECO:0007829|PDB:4IN9"
FT STRAND 131..135
FT /evidence="ECO:0007829|PDB:4IN9"
FT STRAND 140..148
FT /evidence="ECO:0007829|PDB:4IN9"
FT HELIX 149..161
FT /evidence="ECO:0007829|PDB:4IN9"
FT STRAND 174..176
FT /evidence="ECO:0007829|PDB:2XS4"
FT HELIX 186..196
FT /evidence="ECO:0007829|PDB:4IN9"
SQ SEQUENCE 472 AA; 52061 MW; 4950E6623E0150B3 CRC64;
MKRFILLFFL STIAIFKVYS QRLYDNGPLT GDNNYVLQGS KWNKTTLKYY IYNSSSHLTT
TERENAIRSA FALWSDKSTL SFIQVYNPNQ ADIKIKWEKG NHGDGYPFDG NTGILAHAFY
PPPAGGNYAG HLHFDGDENW SINGSGIDLI TVAAHEIGHL LGIEHSNVSS ALMYPYYTGI
KRQLDNDDCL AVWDLYGYPF SISGPSSVCD QATYTVENLL SGATVQWSVS NPNIATINSS
NGVLTCRGNG ICEVRATINN SSVALTPLKI CLGTPISQDI TLTVESLNSN GTLCTDNPNA
IMADHPGGNH LGYIREYEWR ISNGWQIAHH PGDNGIYADH FIVTVIPLSP LPGSPTVSVR
ARSECGWGTW KEVQIPAVSC SRTISPFTLS PNPATDEVIL QLMETDEVSG LSVLSTDRSA
YEIQIWSGMR MLRSFRTNEP TFQISMTGLP AGLYFVRVVK NGQTYTQKLI KK
