ID THER_BACCL Reviewed; 546 AA. AC Q59193; DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 03-MAY-2023, entry version 96. DE RecName: Full=Thermolysin; DE EC=3.4.24.27; DE AltName: Full=Thermostable neutral proteinase; DE Flags: Precursor; GN Name=npr; OS Bacillus caldolyticus. OC Bacteria; Bacillota; Bacilli; Bacillales; Bacillaceae; Geobacillus; OC Geobacillus thermoleovorans group. OX NCBI_TaxID=1394; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=DSM 405 / NBRC 15313 / YP-T; RX PubMed=8765753; DOI=10.1016/0167-4781(96)00074-7; RA Saul D.J., Williams L.C., Toogood H.S., Daniel R.M., Bergquist P.L.; RT "Sequence of the gene encoding a highly thermostable neutral proteinase RT from Bacillus sp. strain EA1: expression in Escherichia coli and RT characterisation."; RL Biochim. Biophys. Acta 1308:74-80(1996). CC -!- FUNCTION: Extracellular zinc metalloprotease. CC -!- CATALYTIC ACTIVITY: CC Reaction=Preferential cleavage: Xaa-|-Leu > Xaa-|-Phe.; EC=3.4.24.27; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Note=Binds 4 Ca(2+) ions per subunit.; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Note=Binds 1 zinc ion per subunit.; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Temperature dependence: CC Thermostable.; CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- SIMILARITY: Belongs to the peptidase M4 family. {ECO:0000305}. 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; U25629; AAB18652.1; -; Genomic_DNA. DR PIR; S72176; S72176. DR AlphaFoldDB; Q59193; -. DR SMR; Q59193; -. DR MEROPS; M04.018; -. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. DR CDD; cd09597; M4_TLP; 1. DR Gene3D; 3.10.170.10; -; 1. DR Gene3D; 3.10.450.40; -; 1. DR Gene3D; 3.10.450.490; -; 1. DR Gene3D; 1.10.390.10; Neutral Protease Domain 2; 1. DR InterPro; IPR011096; FTP_domain. DR InterPro; IPR025711; PepSY. DR InterPro; IPR023612; Peptidase_M4. DR InterPro; IPR027268; Peptidase_M4/M1_CTD_sf. DR InterPro; IPR001570; Peptidase_M4_C_domain. DR InterPro; IPR013856; Peptidase_M4_domain. DR PANTHER; PTHR33794; BACILLOLYSIN; 1. DR PANTHER; PTHR33794:SF3; NEUTRAL PROTEASE B; 1. DR Pfam; PF07504; FTP; 1. DR Pfam; PF03413; PepSY; 1. DR Pfam; PF01447; Peptidase_M4; 1. DR Pfam; PF02868; Peptidase_M4_C; 1. DR PRINTS; PR00730; THERMOLYSIN. DR SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1. DR PROSITE; PS00142; ZINC_PROTEASE; 1. PE 1: Evidence at protein level; KW Calcium; Hydrolase; Metal-binding; Metalloprotease; Protease; Secreted; KW Signal; Zinc; Zymogen. FT SIGNAL 1..25 FT /evidence="ECO:0000255" FT PROPEP 26..228 FT /note="Activation peptide" FT /id="PRO_0000028586" FT CHAIN 229..546 FT /note="Thermolysin" FT /id="PRO_0000028587" FT ACT_SITE 373 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095" FT ACT_SITE 461 FT /note="Proton donor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095" FT BINDING 287 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 289 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 291 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 368 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 372 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095" FT BINDING 376 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095" FT BINDING 396 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095" FT BINDING 413 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250" FT BINDING 415 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 415 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250" FT BINDING 417 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 420 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 420 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250" FT BINDING 423 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000250" FT BINDING 424 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000250" FT BINDING 427 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000250" FT BINDING 430 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000250" SQ SEQUENCE 546 AA; 59771 MW; 38019807FF32B071 CRC64; MDKRAMLGAI GLAFGLMAWP FGASAKEKSM VWNEQWKTPS FVSGSLLKGE DAPEELVYRY LDQEKNTFQL GGQARERLSL IGKQTDELGH TVMRFEQRYR GIPVYGAVLV AHVNDGELSS LSGTLIPNLD KRTLKTEAAI SIQQAEMIAK QDVADAVTKE RPAAEEGKPT RLVIYPDGET PRLAYEVNVR FLTPVPGNWI YMIDAADGKV LNKWNQMDEA KPGGGQPVAG TSTVGVGRGV LGDQKYINTT YSSYYGYYYL QDNTRGSGIF TYDGRNRTVL PGSLWADGDN QFFASYDAAA VDAHYYAGVV YDYYKNVHGR LSYDGSNAAI RSTVHYGRGY NNAFWNGSQM VYGDGDGQTF LPFSGGIDVV GHELTHAVTD YTAGLVYQNE SGAINEAMSD IFGTLVEFYA NRNPDWEIGE DIYTPGIAGD ALRSMSDPAK YGDPDHYSKR YTGTQDNGGV HTNSGIINKA AYLLSQGGVH YGVSVTGIGR DKMGKIFYRA LVYYLTPTSN FSQLRAACVQ AAADLYGSTS QEVNSVKQAF NAVGVY //