ID COLG_HATHI Reviewed; 1118 AA. AC Q9X721; Q9S0X0; DT 28-MAR-2018, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1999, sequence version 1. DT 24-JAN-2024, entry version 113. DE RecName: Full=Collagenase ColG {ECO:0000303|PubMed:9922257}; DE EC=3.4.24.3 {ECO:0000269|PubMed:3002446}; DE AltName: Full=Class I collagenase {ECO:0000303|PubMed:6087888, ECO:0000303|PubMed:9922257}; DE AltName: Full=Gelatinase ColG {ECO:0000303|PubMed:9922257}; DE AltName: Full=Microbial collagenase; DE Flags: Precursor; GN Name=colG {ECO:0000303|PubMed:9922257}; OS Hathewaya histolytica (Clostridium histolyticum). OC Bacteria; Bacillota; Clostridia; Eubacteriales; Clostridiaceae; Hathewaya. OX NCBI_TaxID=1498; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 111-150, FUNCTION, RP SUBCELLULAR LOCATION, INDUCTION, DOMAIN, AND PROTEIN CLEAVAGE. RC STRAIN=ATCC 19401 / DSM 2158 / JCM 1403 / NCIMB 503 / NCTC 503; RX PubMed=9922257; DOI=10.1128/jb.181.3.923-933.1999; RA Matsushita O., Jung C.-M., Katayama S., Minami J., Takahashi Y., Okabe A.; RT "Gene duplication and multiplicity of collagenases in Clostridium RT histolyticum."; RL J. Bacteriol. 181:923-933(1999). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 19401 / DSM 2158 / JCM 1403 / NCIMB 503 / NCTC 503; RA Hosaka T., Yamato I.; RT "Class 1 collagenase."; RL Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases. RN [3] RP COFACTOR, AND CLASSIFICATION. RX PubMed=6087888; DOI=10.1021/bi00308a036; RA Bond M.D., Van Wart H.E.; RT "Characterization of the individual collagenases from Clostridium RT histolyticum."; RL Biochemistry 23:3085-3091(1984). RN [4] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=3002446; DOI=10.1021/bi00344a033; RA Mookhtiar K.A., Steinbrink D.R., Van Wart H.E.; RT "Mode of hydrolysis of collagen-like peptides by class I and class II RT Clostridium histolyticum collagenases: evidence for both endopeptidase and RT tripeptidylcarboxypeptidase activities."; RL Biochemistry 24:6527-6533(1985). RN [5] RP PRELIMINARY STUDIES FOR PHARMACEUTICAL USE FOR TREATMENT OF PEYRONIE RP DISEASE. RX PubMed=8417217; DOI=10.1016/s0022-5347(17)35998-0; RA Gelbard M.K., James K., Riach P., Dorey F.; RT "Collagenase versus placebo in the treatment of Peyronie's disease: a RT double-blind study."; RL J. Urol. 149:56-58(1993). RN [6] RP BIOTECHNOLOGY USE IN TREATING RETAINED PLACENTA. RX PubMed=9699958; DOI=10.1016/s0143-4004(98)90077-7; RA Fecteau K.A., Haffner J.C., Eiler H.; RT "The potential of collagenase as a new therapy for separation of human RT retained placenta: hydrolytic potency on human, equine and bovine RT placentae."; RL Placenta 19:379-383(1998). RN [7] RP PHARMACEUTICAL USE FOR TREATMENT OF DUPUYTREN DISEASE. RX PubMed=10913202; DOI=10.1053/jhsu.2000.6918; RA Badalamente M.A., Hurst L.C.; RT "Enzyme injection as nonsurgical treatment of Dupuytren's disease."; RL J. Hand Surg. Am. 25:629-636(2000). RN [8] RP FUNCTION, DOMAIN, AND COLLAGEN-BINDING. RX PubMed=11913772; DOI=10.3109/03008200109016842; RA Toyoshima T., Matsushita O., Minami J., Nishi N., Okabe A., Itano T.; RT "Collagen-binding domain of a Clostridium histolyticum collagenase exhibits RT a broad substrate spectrum both in vitro and in vivo."; RL Connect. Tissue Res. 42:281-290(2001). RN [9] RP FUNCTION, POSSIBLE ACTIVE SITE, DOMAIN, COLLAGEN-BINDING, AND MUTAGENESIS RP OF GLU-524. RX PubMed=11121400; DOI=10.1074/jbc.m003450200; RA Matsushita O., Koide T., Kobayashi R., Nagata K., Okabe A.; RT "Substrate recognition by the collagen-binding domain of Clostridium RT histolyticum class I collagenase."; RL J. Biol. Chem. 276:8761-8770(2001). RN [10] RP FUNCTION, SUBCELLULAR LOCATION, AND BIOTECHNOLOGY FOR ISOLATION OF PANCREAS RP ISLET CELLS. RX PubMed=18374061; DOI=10.1016/j.transproceed.2008.01.041; RA McCarthy R.C., Spurlin B., Wright M.J., Breite A.G., Sturdevant L.K., RA Dwulet C.S., Dwulet F.E.; RT "Development and characterization of a collagen degradation assay to assess RT purified collagenase used in islet isolation."; RL Transplant. Proc. 40:339-342(2008). RN [11] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL RP PROPERTIES, AND DOMAIN. RX PubMed=18937627; DOI=10.1515/bc.2009.004; RA Eckhard U., Schoenauer E., Ducka P., Briza P., Nuess D., Brandstetter H.; RT "Biochemical characterization of the catalytic domains of three different RT Clostridial collagenases."; RL Biol. Chem. 390:11-18(2009). RN [12] RP COLLAGEN BINDING BY S3B DOMAIN. RX PubMed=19208618; DOI=10.1074/jbc.m807684200; RA Philominathan S.T., Koide T., Hamada K., Yasui H., Seifert S., RA Matsushita O., Sakon J.; RT "Unidirectional binding of clostridial collagenase to triple helical RT substrates."; RL J. Biol. Chem. 284:10868-10876(2009). RN [13] RP PHARMACEUTICAL USES FOR WOUND TREATMENT AND BURN DEBRIDEMENT. RX PubMed=19918145; DOI=10.1097/won.0b013e3181bfdd1a; RA Shi L., Carson D.; RT "Collagenase Santyl ointment: a selective agent for wound debridement."; RL J. Wound Ostomy Continence Nurs. 36:S12-S16(2009). RN [14] RP PHARMACEUTICAL USES FOR TREATMENT OF DUPUYTREN DISEASE. RX PubMed=19726771; DOI=10.1056/nejmoa0810866; RG CORD I Study Group; RA Hurst L.C., Badalamente M.A., Hentz V.R., Hotchkiss R.N., Kaplan F.T., RA Meals R.A., Smith T.M., Rodzvilla J.; RT "Injectable collagenase clostridium histolyticum for Dupuytren's RT contracture."; RL N. Engl. J. Med. 361:968-979(2009). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, SUBCELLULAR LOCATION, RP PROTEIN CLEAVAGE, AND BIOTECHNOLOGY FOR ISOLATION OF PANCREAS ISLET CELLS. RX PubMed=22099748; DOI=10.1016/j.transproceed.2011.09.059; RA Breite A.G., McCarthy R.C., Dwulet F.E.; RT "Characterization and functional assessment of Clostridium histolyticum RT class I (C1) collagenases and the synergistic degradation of native RT collagen in enzyme mixtures containing class II (C2) collagenase."; RL Transplant. Proc. 43:3171-3175(2011). RN [16] RP COLLAGEN BINDING BY S3B DOMAIN. RX PubMed=22898990; DOI=10.1002/pro.2145; RA Philominathan S.T., Koide T., Matsushita O., Sakon J.; RT "Bacterial collagen-binding domain targets undertwisted regions of RT collagen."; RL Protein Sci. 21:1554-1565(2012). RN [17] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=24125730; DOI=10.1016/j.jprot.2013.10.004; RA Eckhard U., Huesgen P.F., Brandstetter H., Overall C.M.; RT "Proteomic protease specificity profiling of clostridial collagenases RT reveals their intrinsic nature as dedicated degraders of collagen."; RL J. Proteomics 100:102-114(2014). RN [18] RP PHARMACEUTICAL USE FOR TREATMENT OF PEYRONIE DISEASE. RX PubMed=25711400; DOI=10.1111/bju.13096; RA Lipshultz L.I., Goldstein I., Seftel A.D., Kaufman G.J., Smith T.M., RA Tursi J.P., Burnett A.L.; RT "Clinical efficacy of collagenase Clostridium histolyticum in the treatment RT of Peyronie's disease by subgroup: results from two large, double-blind, RT randomized, placebo-controlled, phase III studies."; RL BJU Int. 116:650-656(2015). RN [19] RP FUNCTION, ACTIVITY REGULATION, AND BIOTECHNOLOGY FOR ANTI-INFECTIVE AGENTS. RX PubMed=28820255; DOI=10.1021/jacs.7b06935; RA Schoenauer E., Kany A.M., Haupenthal J., Huesecken K., Hoppe I.J., Voos K., RA Yahiaoui S., Elsaesser B., Ducho C., Brandstetter H., Hartmann R.W.; RT "Discovery of a potent inhibitor class with high selectivity toward RT clostridial collagenases."; RL J. Am. Chem. Soc. 139:12696-12703(2017). RN [20] {ECO:0007744|PDB:1NQD, ECO:0007744|PDB:1NQJ} RP X-RAY CRYSTALLOGRAPHY (1.00 ANGSTROMS) OF 1003-1118 IN THE PRESENCE AND RP ABSENCE OF CALCIUM, CALCIUM COFACTOR, DOMAIN, COLLAGEN-BINDING, AND RP MUTAGENESIS OF ARG-1039; PHE-1062; THR-1067; TYR-1080; VAL-1088; LEU-1102; RP TYR-1104 AND TYR-1106. RX PubMed=12682007; DOI=10.1093/emboj/cdg172; RA Wilson J.J., Matsushita O., Okabe A., Sakon J.; RT "A bacterial collagen-binding domain with novel calcium-binding motif RT controls domain orientation."; RL EMBO J. 22:1743-1752(2003). RN [21] {ECO:0007744|PDB:2O8O} RP X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 1003-1118 IN COMPLEX WITH RP CALCIUM. RA Philominathan S.T.L., Wilson J.J., Matsushita O., Sakon J.; RT "Induction of stable beta-sheet by Ca2+ in Clostridial collagen binding RT domain."; RL Submitted (DEC-2006) to the PDB data bank. RN [22] {ECO:0007744|PDB:2Y72} RP X-RAY CRYSTALLOGRAPHY (1.18 ANGSTROMS) OF 799-880, AND DOMAIN. RX PubMed=21871007; DOI=10.1515/bc.2011.099; RA Eckhard U., Brandstetter H.; RT "Polycystic kidney disease-like domains of clostridial collagenases and RT their role in collagen recruitment."; RL Biol. Chem. 392:1039-1045(2011). RN [23] {ECO:0007744|PDB:2Y3U, ECO:0007744|PDB:2Y50, ECO:0007744|PDB:2Y6I, ECO:0007744|PDB:2Y72} RP X-RAY CRYSTALLOGRAPHY (1.18 ANGSTROMS) OF 799-880, X-RAY CRYSTALLOGRAPHY RP (2.80 ANGSTROMS) OF 119-880 IN COMPLEX WITH AND WITHOUT ZINC, X-RAY RP CRYSTALLOGRAPHY (3.25 ANGSTROMS) OF 119-880 IN COMPLEX WITH ZINC AND AN RP INHIBITOR, FUNCTION, REACTION MECHANISM, ZINC COFACTOR, ACTIVITY RP REGULATION, DOMAIN, AND MUTAGENESIS OF 389-GLY--VAL-397. RX PubMed=21947205; DOI=10.1038/nsmb.2127; RA Eckhard U., Schonauer E., Nuss D., Brandstetter H.; RT "Structure of collagenase G reveals a chew-and-digest mechanism of RT bacterial collagenolysis."; RL Nat. Struct. Mol. Biol. 18:1109-1114(2011). RN [24] {ECO:0007744|PDB:4HPK} RP X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 1006-1118 AND 1002-1118 IN RP COMPLEX WITH CALCIUM, COFACTOR, DOMAIN, AND COLLAGEN-BINDING. RX PubMed=23144249; DOI=10.1128/jb.00010-12; RA Bauer R., Wilson J.J., Philominathan S.T., Davis D., Matsushita O., RA Sakon J.; RT "Structural comparison of ColH and ColG collagen-binding domains from RT Clostridium histolyticum."; RL J. Bacteriol. 195:318-327(2013). RN [25] {ECO:0007744|PDB:4AQO, ECO:0007744|PDB:4ARE} RP X-RAY CRYSTALLOGRAPHY (0.99 ANGSTROMS) OF 792-880 IN COMPLEX WITH CALCIUM, RP X-RAY CRYSTALLOGRAPHY (2.19 ANGSTROMS) OF 119-789 IN COMPLEX WITH ZINC, RP FUNCTION, COFACTOR, AND DOMAIN. RX PubMed=23703618; DOI=10.1074/jbc.m112.448548; RA Eckhard U., Schonauer E., Brandstetter H.; RT "Structural basis for activity regulation and substrate preference of RT clostridial collagenases G, H, and T."; RL J. Biol. Chem. 288:20184-20194(2013). RN [26] {ECO:0007744|PDB:4JRW, ECO:0007744|PDB:4TN9} RP X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF 797-881, AND DOMAIN. RX PubMed=25760606; DOI=10.1107/s1399004714027722; RA Bauer R., Janowska K., Taylor K., Jordan B., Gann S., Janowski T., RA Latimer E.C., Matsushita O., Sakon J.; RT "Structures of three polycystic kidney disease-like domains from RT Clostridium histolyticum collagenases ColG and ColH."; RL Acta Crystallogr. D 71:565-577(2015). RN [27] {ECO:0007744|PDB:5IKU} RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 883-1118 IN COMPLEX WITH CALCIUM, RP COFACTOR, AND DOMAIN. RA Janowska K., Bauer R., Roeser R., Sakon J., Matsushita O.; RT "Crystal structure of the Clostridium histolyticum ColG tandem collagen- RT binding domain s3as3b in the presence of calcium at 1.9 Angstrom RT resolution."; RL Submitted (MAR-2016) to the PDB data bank. CC -!- FUNCTION: Clostridial collagenases are among the most efficient CC degraders of eukaryotic collagen known; saprophytes use collagen as a CC carbon source while pathogens additionally digest collagen to aid in CC host colonization. Has both tripeptidylcarboxypeptidase on Gly-X-Y and CC endopeptidase activities; the endopeptidase cuts within the triple CC helix region of collagen while tripeptidylcarboxypeptidase successively CC digests the exposed ends, thus clostridial collagenases can digest CC large sections of collagen (PubMed:3002446). Active on soluble type I CC collagen, insoluble collagen, azocoll, soluble PZ-peptide (all CC collagenase substrates) and gelatin (PubMed:9922257). The full-length CC protein has collagenase activity, while the in vivo derived C- CC terminally truncated shorter versions only act on gelatin CC (PubMed:9922257). In vitro digestion of soluble calf skin collagen CC fibrils requires both ColG and ColH; ColG forms missing the second CC collagen-binding domain are also synergistic with ColH, although their CC overall efficiency is decreased (PubMed:18374061, PubMed:22099748). The CC activator domain (residues 119-388) and catalytic subdomain (389-670) CC open and close around substrate using a Gly-rich hinge (387-397), CC allowing digestion when the protein is closed (PubMed:21947205, CC PubMed:23703618). Binding of collagen requires Ca(2+) and is inhibited CC by EGTA; the collagen-binding domain (CBD, S3a plus S3b) specifically CC recognizes the triple-helical conformation made by 3 collagen protein CC chains in the triple-helical region (PubMed:11121400). Isolated CBD CC (S3a plus S3b) binds collagen fibrils and sheets of many tissues CC (PubMed:11913772). {ECO:0000269|PubMed:11121400, CC ECO:0000269|PubMed:11913772, ECO:0000269|PubMed:18374061, CC ECO:0000269|PubMed:18937627, ECO:0000269|PubMed:21947205, CC ECO:0000269|PubMed:22099748, ECO:0000269|PubMed:23703618, CC ECO:0000269|PubMed:24125730, ECO:0000269|PubMed:28820255, CC ECO:0000269|PubMed:3002446, ECO:0000269|PubMed:9922257}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Digestion of native collagen in the triple helical region at CC Xaa-|-Gly bonds. With synthetic peptides, a preference is shown for CC Gly at P3 and P1', Pro and Ala at P2 and P2', and hydroxyproline, Ala CC or Arg at P3'.; EC=3.4.24.3; Evidence={ECO:0000269|PubMed:24125730, CC ECO:0000269|PubMed:3002446, ECO:0000305|PubMed:18937627}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000269|PubMed:12682007, ECO:0000269|PubMed:23144249, CC ECO:0000269|PubMed:23703618, ECO:0000269|PubMed:6087888, CC ECO:0000269|Ref.21, ECO:0000269|Ref.27}; CC Note=Binds about 7 Ca(2+) per subunit (PubMed:6087888). The CC metallopeptidase and PKD domains each bind 1 Ca(2+), while each CDB CC binds 2 (PubMed:12682007, Ref.21, PubMed:23144249, Ref.27). CC {ECO:0000269|PubMed:12682007, ECO:0000269|PubMed:23144249, CC ECO:0000269|PubMed:6087888, ECO:0000269|Ref.21, ECO:0000269|Ref.27}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000269|PubMed:21947205, ECO:0000269|PubMed:23703618, CC ECO:0000269|PubMed:6087888}; CC Note=Binds 1 catalytic Zn(2+) per subunit, a Zn-free form has been CC crystallized (PubMed:21947205). {ECO:0000269|PubMed:21947205, CC ECO:0000269|PubMed:23703618, ECO:0000269|PubMed:6087888}; CC -!- ACTIVITY REGULATION: Inhibited by 1-10-phenanthroline CC (PubMed:18937627). Inhibited by peptidomimetic isoamyl-phosphonyl-Gly- CC Pro-Ala, which binds to Zn(2+) (PubMed:21947205). Inhibited by broad- CC spectrum zinc metalloprotease inhibitor batimastat (PubMed:28820255). CC N-aryl mercaptoacetamide-based inhibitors have been isolated that act CC on clostridial collagenases with submicromolar affinity while having CC negligibile activity on human collagenases (PubMed:28820255). CC {ECO:0000269|PubMed:18937627, ECO:0000269|PubMed:21947205, CC ECO:0000269|PubMed:28820255}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.84 mM for furylacryloyl-Leu-Gly-Pro-Ala (FALGPA) CC {ECO:0000269|PubMed:18937627}; CC Vmax=0.0852 umol/min/mg enzyme {ECO:0000269|PubMed:18937627}; CC Note=kcat is 0.11/sec, using a catalytic fragment (119-790) on an CC artificial substrate. {ECO:0000269|PubMed:18937627}; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:18374061, CC ECO:0000269|PubMed:22099748, ECO:0000269|PubMed:9922257}. CC -!- INDUCTION: RNA levels are high in late logarithmic phase. CC {ECO:0000269|PubMed:9922257}. CC -!- DOMAIN: The mature protein has 4 domains; a metalloprotease domain (S1, CC approximately residues 111-786), S2 (877-882, equivalent to PKD), and 2 CC collagen-binding domains (CBD) S3a (997-1003) and S3b (1008-1118) CC (PubMed:9922257, PubMed:11121400). The S1 domain has collagen CC hydrolytic activity (PubMed:11121400, PubMed:18937627). The CC metalloprotease S1 domain is composed of 3 subdomains which together CC resemble a saddle; an activator domain (residues 119-388), the CC catalytic peptidase subdomain (398-670) and a helper subdomain (679- CC 790) joined by a Gly-rich hinge (387-397) (PubMed:21947205, CC PubMed:23703618). The S2 domain (799-880, PKD) is flexible within a CC larger structure (S1 plus S2, residues 119-880) (PubMed:21947205, CC PubMed:21871007). Binding to Ca(2+) renders the midsection of S2 more CC flexible; Ca(2+) binding confers thermostability (PubMed:25760606). S3a CC and S3b each have collagen-binding activity; collagen is bound more CC efficiently when both S3a and S3b are present (PubMed:11121400). CBD CC S3a plus S3b binds to many types of collagen in vitro and in vivo CC (PubMed:11913772). The structure of CBD S3b becomes more compact and CC thermostable when it is bound to Ca(2+) and its N-terminal linker CC (approximately residues 1008-1020) changes from an extended alpha-helix CC to a beta-sheet anchored to the rest of the CBD (PubMed:12682007, CC PubMed:23144249). S3b may act as a Ca(2+)-activated molecular switch to CC trigger domain reorientation (PubMed:12682007). Isolated CBD S3b binds CC unidirectionally to the C-terminus of the collagen triple helix via a CC surface cleft (PubMed:19208618, PubMed:23144249). The S3b domain binds CC preferentially to undertwisted segions of collagen (PubMed:22898990). CC {ECO:0000269|PubMed:11121400, ECO:0000269|PubMed:11913772, CC ECO:0000269|PubMed:12682007, ECO:0000269|PubMed:18937627, CC ECO:0000269|PubMed:19208618, ECO:0000269|PubMed:21947205, CC ECO:0000269|PubMed:22898990, ECO:0000269|PubMed:23144249, CC ECO:0000269|PubMed:23703618, ECO:0000269|PubMed:25760606, CC ECO:0000305|PubMed:11121400, ECO:0000305|PubMed:21871007, CC ECO:0000305|PubMed:23144249, ECO:0000305|PubMed:9922257}. CC -!- PTM: Upon purification gives 67 kDa, 78 kDa, 82 kDa and 116 kDa (full- CC length) proteins all of which have the same N-terminus; only the CC longest form digests insoluble collagen (PubMed:9922257). At least 2 in CC vivo isolated forms (C1b and C1c) are missing the second collagen- CC binding domain, ending on Lys-1006 and Lys-1018 respectively CC (PubMed:22099748). {ECO:0000269|PubMed:22099748, CC ECO:0000269|PubMed:9922257}. CC -!- BIOTECHNOLOGY: Widely used for tissue dissociation due to their potent CC activity on connective tissue. {ECO:0000305}. CC -!- BIOTECHNOLOGY: A mix of ColG and ColH is used for isolation of CC pancreatic islet cells for subsequent transplantation. CC {ECO:0000269|PubMed:18374061, ECO:0000269|PubMed:22099748}. CC -!- BIOTECHNOLOGY: A mix of ColG and ColH has been used to allow release of CC retained placenta in cows and mares, and its use in humans has been CC proposed. {ECO:0000269|PubMed:9699958}. CC -!- BIOTECHNOLOGY: N-aryl mercaptoacetamide-based inhibitors with CC submicromolar affinity for clostridial collagenases but negligibile CC activity on human collagenases have been discovered that may lead to CC promising anti-infective drugs against Clostridia (PubMed:28820255). CC {ECO:0000269|PubMed:28820255}. CC -!- PHARMACEUTICAL: SANTYL Ointment (Smith and Nephew, Inc.) is indicated CC for debriding chronic dermal ulcers and severely burned areas. It is CC unclear which of the collagenases from this bacteria is in the CC ointment. {ECO:0000269|PubMed:19918145}. CC -!- PHARMACEUTICAL: Xiaflex (Endo Pharmaceuticals, Inc.) is a mix of CC H.histolytica collagenases (ColG and ColH) used to treat both Dupuytren CC disease and Peyronie disease. Dupuytren disease is a progressive CC genetic disorder of pathologic collagen production and deposition under CC the skin of the hand that causes the fingers to be drawn into the palm, CC leading to flexion contractures of the joints, which can severely limit CC hand function. Injections of collagenase reduce these joint CC contractures (PubMed:10913202, PubMed:19726771). Peyronie disease (PD) CC is characterized by a disorganized, excessive deposition of collagen CC that forms a plaque within the penis. The plaque restricts lengthening CC on the affected side during erection, which can lead to penile CC curvature deformity, discomfort and erectile dysfunction, and can CC eventually lead to psychosocial effects such as depression and CC relationship difficulties. Studies have shown the clinical efficacy of CC collagenase injection for reducing penile curvature deformity and CC psychosocial symptoms (PubMed:8417217, PubMed:25711400). CC {ECO:0000269|PubMed:10913202, ECO:0000269|PubMed:19726771, CC ECO:0000269|PubMed:25711400, ECO:0000269|PubMed:8417217}. CC -!- MISCELLANEOUS: Clostridial collagenases enable the bacteria to CC infiltrate and colonize host tissue, and contribute to gas gangrene CC (myonecrosis) pathogenesis. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the peptidase M9B family. Collagenase subfamily. CC {ECO:0000305|PubMed:6087888, ECO:0000305|PubMed:9922257}. CC -!- WEB RESOURCE: Name=Worthington enzyme manual; CC URL="https://www.worthington-biochem.com/CLS/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; D87215; BAA77453.1; -; Genomic_DNA. DR EMBL; AB026889; BAA86030.1; -; Genomic_DNA. DR PDB; 1NQD; X-ray; 1.65 A; A/B=1003-1118. DR PDB; 1NQJ; X-ray; 1.00 A; A/B=1003-1118. DR PDB; 2O8O; X-ray; 1.35 A; A/B=1003-1118. DR PDB; 2Y3U; X-ray; 2.55 A; A=119-880. DR PDB; 2Y50; X-ray; 2.80 A; A=119-880. DR PDB; 2Y6I; X-ray; 3.25 A; A=119-880. DR PDB; 2Y72; X-ray; 1.18 A; A/B=799-880. DR PDB; 4AQO; X-ray; 0.99 A; A=792-880. DR PDB; 4ARE; X-ray; 2.19 A; A=119-789. DR PDB; 4HPK; X-ray; 1.35 A; A=1006-1118, B=1003-1118. DR PDB; 4JRW; X-ray; 1.60 A; A/B=797-881. DR PDB; 4TN9; X-ray; 1.40 A; A/B=797-881. DR PDB; 5IKU; X-ray; 1.90 A; A=883-1118. DR PDB; 7Z5U; X-ray; 1.80 A; A=398-790. DR PDB; 7ZBV; X-ray; 1.95 A; A=398-790. DR PDBsum; 1NQD; -. DR PDBsum; 1NQJ; -. DR PDBsum; 2O8O; -. DR PDBsum; 2Y3U; -. DR PDBsum; 2Y50; -. DR PDBsum; 2Y6I; -. DR PDBsum; 2Y72; -. DR PDBsum; 4AQO; -. DR PDBsum; 4ARE; -. DR PDBsum; 4HPK; -. DR PDBsum; 4JRW; -. DR PDBsum; 4TN9; -. DR PDBsum; 5IKU; -. DR PDBsum; 7Z5U; -. DR PDBsum; 7ZBV; -. DR AlphaFoldDB; Q9X721; -. DR SASBDB; Q9X721; -. DR SMR; Q9X721; -. DR BindingDB; Q9X721; -. DR ChEMBL; CHEMBL2268009; -. DR Allergome; 5989; Clo hi Collagenase. DR MEROPS; M09.002; -. DR OrthoDB; 9798386at2; -. DR BRENDA; 3.4.24.3; 1481. DR EvolutionaryTrace; Q9X721; -. DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB. DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB. DR GO; GO:0005518; F:collagen binding; IDA:UniProtKB. DR GO; GO:0004175; F:endopeptidase activity; IDA:UniProtKB. DR GO; GO:0004222; F:metalloendopeptidase activity; IMP:UniProtKB. DR GO; GO:0034701; F:tripeptidase activity; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB. DR GO; GO:0032963; P:collagen metabolic process; IDA:UniProtKB. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. DR CDD; cd00146; PKD; 1. DR Gene3D; 1.10.390.20; -; 1. DR Gene3D; 2.60.120.380; -; 2. DR Gene3D; 3.30.980.50; -; 1. DR Gene3D; 3.40.30.160; Collagenase ColT, N-terminal domain; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 1. DR InterPro; IPR041379; ColG_subdomain. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR007280; Peptidase_C_arc/bac. DR InterPro; IPR013661; Peptidase_M9_N_dom. DR InterPro; IPR002169; Peptidase_M9A/M9B. DR InterPro; IPR022409; PKD/Chitinase_dom. DR InterPro; IPR000601; PKD_dom. DR InterPro; IPR035986; PKD_dom_sf. DR PANTHER; PTHR13062:SF9; A2M DOMAIN-CONTAINING PROTEIN; 1. DR PANTHER; PTHR13062; COLLAGENASE; 1. DR Pfam; PF18496; ColG_sub; 1. DR Pfam; PF01752; Peptidase_M9; 1. DR Pfam; PF08453; Peptidase_M9_N; 1. DR Pfam; PF18911; PKD_4; 1. DR Pfam; PF04151; PPC; 1. DR PRINTS; PR00931; MICOLLPTASE. DR SMART; SM00089; PKD; 1. DR SUPFAM; SSF89260; Collagen-binding domain; 2. DR SUPFAM; SSF49299; PKD domain; 1. DR PROSITE; PS50093; PKD; 1. DR PROSITE; PS00142; ZINC_PROTEASE; 1. PE 1: Evidence at protein level; KW 3D-structure; Calcium; Direct protein sequencing; Hydrolase; Metal-binding; KW Metalloprotease; Pharmaceutical; Protease; Repeat; Secreted; Signal; KW Virulence; Zinc; Zymogen. FT SIGNAL 1..45 FT /evidence="ECO:0000255" FT PROPEP 46..110 FT /evidence="ECO:0000305|PubMed:9922257" FT /id="PRO_0000443545" FT CHAIN 111..1118 FT /note="Collagenase ColG" FT /id="PRO_0000443546" FT DOMAIN 797..885 FT /note="PKD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00151" FT REGION 111..786 FT /note="S1 metalloprotease domain, degrades both FALGPA FT (furylacryloyl-Leu-Gly-Pro-Ala) and type I collagen" FT /evidence="ECO:0000269|PubMed:21947205, FT ECO:0000305|PubMed:11121400, ECO:0000305|PubMed:9922257" FT REGION 119..388 FT /note="Activator domain required for full activity on FT collagen" FT /evidence="ECO:0000269|PubMed:21947205, FT ECO:0000305|PubMed:23703618" FT REGION 389..670 FT /note="Catalytic subdomain" FT /evidence="ECO:0000305|PubMed:23703618" FT REGION 396..1118 FT /note="Degrades soluble FALGPA peptide (furylacryloyl-Leu- FT Gly-Pro-Ala) but not type I collagen" FT /evidence="ECO:0000269|PubMed:21947205" FT REGION 679..790 FT /note="Helper subdomain" FT /evidence="ECO:0000305|PubMed:23703618" FT REGION 787..882 FT /note="S2 domain" FT /evidence="ECO:0000305|PubMed:11121400, FT ECO:0000305|PubMed:9922257" FT REGION 886..1003 FT /note="S3a collagen-binding domain" FT /evidence="ECO:0000305|PubMed:11121400, FT ECO:0000305|PubMed:9922257" FT REGION 1008..1118 FT /note="S3b collagen-binding domain" FT /evidence="ECO:0000269|PubMed:12682007, FT ECO:0000305|PubMed:11121400, ECO:0000305|PubMed:9922257" FT REGION 1102..1106 FT /note="Collagen-binding" FT /evidence="ECO:0000269|PubMed:12682007, FT ECO:0000269|PubMed:19208618" FT ACT_SITE 524 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095, FT ECO:0000305|PubMed:11121400" FT BINDING 498 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q899Y1, FT ECO:0000303|PubMed:23703618" FT BINDING 523 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095, FT ECO:0000269|PubMed:21947205, ECO:0000269|PubMed:23703618, FT ECO:0007744|PDB:2Y50, ECO:0007744|PDB:2Y6I, FT ECO:0007744|PDB:4ARE" FT BINDING 527 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095, FT ECO:0000269|PubMed:21947205, ECO:0000269|PubMed:23703618, FT ECO:0007744|PDB:2Y50, ECO:0007744|PDB:2Y6I, FT ECO:0007744|PDB:4ARE" FT BINDING 531 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q899Y1, FT ECO:0000303|PubMed:23703618" FT BINDING 535 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q899Y1, FT ECO:0000303|PubMed:23703618" FT BINDING 537 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q899Y1, FT ECO:0000303|PubMed:23703618" FT BINDING 555 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:21947205, FT ECO:0000269|PubMed:23703618, ECO:0007744|PDB:2Y50, FT ECO:0007744|PDB:2Y6I, ECO:0007744|PDB:4ARE" FT BINDING 795 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:23703618, FT ECO:0007744|PDB:4AQO" FT BINDING 796 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:23703618, FT ECO:0007744|PDB:4AQO" FT BINDING 823 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:23703618, FT ECO:0007744|PDB:4AQO" FT BINDING 825 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:23703618, FT ECO:0007744|PDB:4AQO" FT BINDING 864 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:23703618, FT ECO:0007744|PDB:4AQO" FT BINDING 890 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0007744|PDB:5IKU" FT BINDING 892 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0007744|PDB:5IKU" FT BINDING 892 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0007744|PDB:5IKU" FT BINDING 894 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0007744|PDB:5IKU" FT BINDING 913 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0007744|PDB:5IKU" FT BINDING 918 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0007744|PDB:5IKU" FT BINDING 918 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0007744|PDB:5IKU" FT BINDING 920 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0007744|PDB:5IKU" FT BINDING 921 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0007744|PDB:5IKU" FT BINDING 921 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0007744|PDB:5IKU" FT BINDING 1009 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000269|PubMed:12682007, FT ECO:0000269|PubMed:23144249, ECO:0007744|PDB:1NQD, FT ECO:0007744|PDB:2O8O, ECO:0007744|PDB:4HPK, FT ECO:0007744|PDB:5IKU" FT BINDING 1011 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000269|PubMed:12682007, FT ECO:0000269|PubMed:23144249, ECO:0007744|PDB:1NQD, FT ECO:0007744|PDB:2O8O, ECO:0007744|PDB:4HPK, FT ECO:0007744|PDB:5IKU" FT BINDING 1011 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="6" FT /evidence="ECO:0000269|PubMed:12682007, FT ECO:0000269|PubMed:23144249, ECO:0007744|PDB:1NQD, FT ECO:0007744|PDB:2O8O, ECO:0007744|PDB:4HPK, FT ECO:0007744|PDB:5IKU" FT BINDING 1013 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="6" FT /evidence="ECO:0000269|PubMed:12682007, FT ECO:0000269|PubMed:23144249, ECO:0007744|PDB:1NQD, FT ECO:0007744|PDB:2O8O, ECO:0007744|PDB:4HPK, FT ECO:0007744|PDB:5IKU" FT BINDING 1014 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="6" FT /evidence="ECO:0000269|PubMed:12682007, FT ECO:0000269|PubMed:23144249, ECO:0007744|PDB:1NQD, FT ECO:0007744|PDB:2O8O, ECO:0007744|PDB:4HPK" FT BINDING 1032 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000269|PubMed:12682007, FT ECO:0000269|PubMed:23144249, ECO:0007744|PDB:1NQD, FT ECO:0007744|PDB:2O8O, ECO:0007744|PDB:4HPK, FT ECO:0007744|PDB:5IKU" FT BINDING 1037 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000269|PubMed:12682007, FT ECO:0000269|PubMed:23144249, ECO:0007744|PDB:1NQD, FT ECO:0007744|PDB:2O8O, ECO:0007744|PDB:4HPK, FT ECO:0007744|PDB:5IKU" FT BINDING 1037 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="6" FT /evidence="ECO:0000269|PubMed:12682007, FT ECO:0000269|PubMed:23144249, ECO:0007744|PDB:1NQD, FT ECO:0007744|PDB:2O8O, ECO:0007744|PDB:4HPK, FT ECO:0007744|PDB:5IKU" FT BINDING 1039 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="6" FT /evidence="ECO:0000269|PubMed:12682007, FT ECO:0000269|PubMed:23144249, ECO:0007744|PDB:1NQD, FT ECO:0007744|PDB:2O8O, ECO:0007744|PDB:4HPK, FT ECO:0007744|PDB:5IKU" FT BINDING 1040 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000269|PubMed:12682007, FT ECO:0000269|PubMed:23144249, ECO:0007744|PDB:1NQD, FT ECO:0007744|PDB:2O8O, ECO:0007744|PDB:4HPK, FT ECO:0007744|PDB:5IKU" FT BINDING 1040 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="6" FT /evidence="ECO:0000269|PubMed:12682007, FT ECO:0000269|PubMed:23144249, ECO:0007744|PDB:1NQD, FT ECO:0007744|PDB:2O8O, ECO:0007744|PDB:4HPK, FT ECO:0007744|PDB:5IKU" FT SITE 1006 FT /note="C-terminus of form C1b" FT /evidence="ECO:0000269|PubMed:22099748" FT SITE 1018 FT /note="C-terminus of form C1c" FT /evidence="ECO:0000269|PubMed:22099748" FT SITE 1067 FT /note="Collagen binding" FT /evidence="ECO:0000269|PubMed:12682007, FT ECO:0000269|PubMed:19208618" FT SITE 1080 FT /note="Collagen binding" FT /evidence="ECO:0000269|PubMed:12682007, FT ECO:0000269|PubMed:19208618" FT MUTAGEN 389..397 FT /note="Missing: Degrades soluble FALGPA peptide FT (furylacryloyl-Leu-Gly-Pro-Ala) but only 40% active on type FT I collagen." FT /evidence="ECO:0000269|PubMed:21947205" FT MUTAGEN 524 FT /note="E->D: Retains 4% digestion of collagen, still bind FT collagen." FT /evidence="ECO:0000269|PubMed:11121400" FT MUTAGEN 1039 FT /note="R->A: S3b fragment has 2.3-fold increased affinity FT for collagen." FT /evidence="ECO:0000269|PubMed:12682007" FT MUTAGEN 1062 FT /note="F->A: S3b fragment has 2.4-fold increased affinity FT for collagen." FT /evidence="ECO:0000269|PubMed:12682007" FT MUTAGEN 1067 FT /note="T->A: S3b fragment has 10-fold decreased affinity FT for collagen." FT /evidence="ECO:0000269|PubMed:12682007" FT MUTAGEN 1080 FT /note="Y->A: S3b fragment has 12-fold decreased affinity FT for collagen." FT /evidence="ECO:0000269|PubMed:12682007" FT MUTAGEN 1088 FT /note="V->A: S3b fragment has 2.2-fold increased affinity FT for collagen." FT /evidence="ECO:0000269|PubMed:12682007" FT MUTAGEN 1102 FT /note="L->A: S3b fragment has 5-fold decreased affinity for FT collagen." FT /evidence="ECO:0000269|PubMed:12682007" FT MUTAGEN 1104 FT /note="Y->A,S: S3b fragment has no collagen binding." FT /evidence="ECO:0000269|PubMed:12682007" FT MUTAGEN 1104 FT /note="Y->F: S3b fragment has 12-fold decreased affinity FT for collagen." FT /evidence="ECO:0000269|PubMed:12682007" FT MUTAGEN 1106 FT /note="Y->A: S3b fragment has 40-fold decreased affinity FT for collagen." FT /evidence="ECO:0000269|PubMed:12682007" FT CONFLICT 606 FT /note="F -> V (in Ref. 2; BAA86030)" FT /evidence="ECO:0000305" FT CONFLICT 656..659 FT /note="EYQN -> DYQT (in Ref. 2; BAA86030)" FT /evidence="ECO:0000305" FT CONFLICT 836..837 FT /note="GD -> VY (in Ref. 2; BAA86030)" FT /evidence="ECO:0000305" FT HELIX 121..124 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 129..137 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 141..143 FT /evidence="ECO:0007829|PDB:4ARE" FT TURN 145..148 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 152..157 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 161..177 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 186..202 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 204..206 FT /evidence="ECO:0007829|PDB:2Y6I" FT HELIX 207..210 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 212..215 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 216..218 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 219..227 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 229..231 FT /evidence="ECO:0007829|PDB:2Y6I" FT HELIX 236..251 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 256..260 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 263..271 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 273..276 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 280..301 FT /evidence="ECO:0007829|PDB:4ARE" FT STRAND 302..304 FT /evidence="ECO:0007829|PDB:2Y3U" FT HELIX 306..308 FT /evidence="ECO:0007829|PDB:4ARE" FT TURN 310..313 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 316..326 FT /evidence="ECO:0007829|PDB:4ARE" FT TURN 333..335 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 336..349 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 350..352 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 356..370 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 374..386 FT /evidence="ECO:0007829|PDB:4ARE" FT STRAND 394..396 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 399..410 FT /evidence="ECO:0007829|PDB:4ARE" FT STRAND 413..417 FT /evidence="ECO:0007829|PDB:4ARE" FT TURN 418..421 FT /evidence="ECO:0007829|PDB:4ARE" FT STRAND 422..426 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 432..453 FT /evidence="ECO:0007829|PDB:4ARE" FT STRAND 459..462 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 464..466 FT /evidence="ECO:0007829|PDB:4ARE" FT STRAND 467..475 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 476..479 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 481..486 FT /evidence="ECO:0007829|PDB:4ARE" FT STRAND 491..497 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 498..500 FT /evidence="ECO:0007829|PDB:4ARE" FT STRAND 502..506 FT /evidence="ECO:0007829|PDB:4ARE" FT TURN 510..512 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 517..533 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 543..545 FT /evidence="ECO:0007829|PDB:4ARE" FT TURN 546..548 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 551..561 FT /evidence="ECO:0007829|PDB:4ARE" FT STRAND 566..568 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 574..580 FT /evidence="ECO:0007829|PDB:4ARE" FT TURN 585..587 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 591..596 FT /evidence="ECO:0007829|PDB:4ARE" FT STRAND 599..601 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 606..620 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 622..633 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 637..649 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 651..667 FT /evidence="ECO:0007829|PDB:4ARE" FT TURN 668..670 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 678..681 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 689..699 FT /evidence="ECO:0007829|PDB:4ARE" FT STRAND 703..711 FT /evidence="ECO:0007829|PDB:4ARE" FT STRAND 716..728 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 732..750 FT /evidence="ECO:0007829|PDB:4ARE" FT HELIX 756..760 FT /evidence="ECO:0007829|PDB:4ARE" FT STRAND 762..770 FT /evidence="ECO:0007829|PDB:4ARE" FT STRAND 775..786 FT /evidence="ECO:0007829|PDB:4ARE" FT STRAND 806..809 FT /evidence="ECO:0007829|PDB:4AQO" FT STRAND 812..817 FT /evidence="ECO:0007829|PDB:4AQO" FT STRAND 824..826 FT /evidence="ECO:0007829|PDB:4TN9" FT STRAND 828..834 FT /evidence="ECO:0007829|PDB:4AQO" FT STRAND 836..838 FT /evidence="ECO:0007829|PDB:4AQO" FT STRAND 840..849 FT /evidence="ECO:0007829|PDB:4AQO" FT STRAND 854..864 FT /evidence="ECO:0007829|PDB:4AQO" FT STRAND 869..879 FT /evidence="ECO:0007829|PDB:4AQO" FT HELIX 897..899 FT /evidence="ECO:0007829|PDB:5IKU" FT STRAND 910..915 FT /evidence="ECO:0007829|PDB:5IKU" FT STRAND 920..927 FT /evidence="ECO:0007829|PDB:5IKU" FT STRAND 929..941 FT /evidence="ECO:0007829|PDB:5IKU" FT STRAND 945..951 FT /evidence="ECO:0007829|PDB:5IKU" FT STRAND 954..957 FT /evidence="ECO:0007829|PDB:5IKU" FT STRAND 959..961 FT /evidence="ECO:0007829|PDB:5IKU" FT STRAND 963..965 FT /evidence="ECO:0007829|PDB:5IKU" FT STRAND 968..975 FT /evidence="ECO:0007829|PDB:5IKU" FT STRAND 977..987 FT /evidence="ECO:0007829|PDB:5IKU" FT STRAND 992..1000 FT /evidence="ECO:0007829|PDB:5IKU" FT HELIX 1007..1018 FT /evidence="ECO:0007829|PDB:1NQJ" FT STRAND 1024..1026 FT /evidence="ECO:0007829|PDB:1NQJ" FT STRAND 1029..1033 FT /evidence="ECO:0007829|PDB:1NQJ" FT STRAND 1039..1048 FT /evidence="ECO:0007829|PDB:1NQJ" FT STRAND 1050..1070 FT /evidence="ECO:0007829|PDB:1NQJ" FT STRAND 1082..1084 FT /evidence="ECO:0007829|PDB:1NQJ" FT STRAND 1087..1094 FT /evidence="ECO:0007829|PDB:1NQJ" FT STRAND 1096..1108 FT /evidence="ECO:0007829|PDB:1NQJ" FT STRAND 1110..1117 FT /evidence="ECO:0007829|PDB:1NQJ" SQ SEQUENCE 1118 AA; 126242 MW; 770CF3F60E4D4FD4 CRC64; MKKNILKILM DSYSKESKIQ TVRRVTSVSL LAVYLTMNTS SLVLAKPIEN TNDTSIKNVE KLRNAPNEEN SKKVEDSKND KVEHVKNIEE AKVEQVAPEV KSKSTLRSAS IANTNSEKYD FEYLNGLSYT ELTNLIKNIK WNQINGLFNY STGSQKFFGD KNRVQAIINA LQESGRTYTA NDMKGIETFT EVLRAGFYLG YYNDGLSYLN DRNFQDKCIP AMIAIQKNPN FKLGTAVQDE VITSLGKLIG NASANAEVVN NCVPVLKQFR ENLNQYAPDY VKGTAVNELI KGIEFDFSGA AYEKDVKTMP WYGKIDPFIN ELKALGLYGN ITSATEWASD VGIYYLSKFG LYSTNRNDIV QSLEKAVDMY KYGKIAFVAM ERITWDYDGI GSNGKKVDHD KFLDDAEKHY LPKTYTFDNG TFIIRAGDKV SEEKIKRLYW ASREVKSQFH RVVGNDKALE VGNADDVLTM KIFNSPEEYK FNTNINGVST DNGGLYIEPR GTFYTYERTP QQSIFSLEEL FRHEYTHYLQ ARYLVDGLWG QGPFYEKNRL TWFDEGTAEF FAGSTRTSGV LPRKSILGYL AKDKVDHRYS LKKTLNSGYD DSDWMFYNYG FAVAHYLYEK DMPTFIKMNK AILNTDVKSY DEIIKKLSDD ANKNTEYQNH IQELADKYQG AGIPLVSDDY LKDHGYKKAS EVYSEISKAA SLTNTSVTAE KSQYFNTFTL RGTYTGETSK GEFKDWDEMS KKLDGTLESL AKNSWSGYKT LTAYFTNYRV TSDNKVQYDV VFHGVLTDNA DISNNKAPIA KVTGPSTGAV GRNIEFSGKD SKDEDGKIVS YDWDFGDGAT SRGKNSVHAY KKAGTYNVTL KVTDDKGATA TESFTIEIKN EDTTTPITKE MEPNDDIKEA NGPIVEGVTV KGDLNGSDDA DTFYFDVKED GDVTIELPYS GSSNFTWLVY KEGDDQNHIA SGIDKNNSKV GTFKSTKGRH YVFIYKHDSA SNISYSLNIK GLGNEKLKEK ENNDSSDKAT VIPNFNTTMQ GSLLGDDSRD YYSFEVKEEG EVNIELDKKD EFGVTWTLHP ESNINDRITY GQVDGNKVSN KVKLRPGKYY LLVYKYSGSG NYELRVNK //