THER_GEOSE
ID THER_GEOSE Reviewed; 551 AA.
AC P43133;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Thermolysin;
DE EC=3.4.24.27;
DE AltName: Full=Neutral protease;
DE Flags: Precursor;
GN Name=nprS; Synonyms=nprM;
OS Geobacillus stearothermophilus (Bacillus stearothermophilus).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae; Geobacillus.
OX NCBI_TaxID=1422;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 236-240, FUNCTION AS
RP A PROTEASE, TEMPERATURE DEPENDENCE, AND SUBCELLULAR LOCATION.
RC STRAIN=MK232;
RX PubMed=3149972; DOI=10.1099/00221287-134-7-1883;
RA Kubo M., Imanaka T.;
RT "Cloning and nucleotide sequence of the highly thermostable neutral
RT protease gene from Bacillus stearothermophilus.";
RL J. Gen. Microbiol. 134:1883-1892(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 236-239, AND
RP INDUCTION.
RC STRAIN=TELNE;
RX PubMed=2203733; DOI=10.1128/jb.172.9.4861-4869.1990;
RA Nishiya Y., Imanaka T.;
RT "Cloning and nucleotide sequences of the Bacillus stearothermophilus
RT neutral protease gene and its transcriptional activator gene.";
RL J. Bacteriol. 172:4861-4869(1990).
CC -!- FUNCTION: Extracellular zinc metalloprotease.
CC {ECO:0000269|PubMed:3149972}.
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; Evidence={ECO:0000250};
CC Note=Binds 4 Ca(2+) ions per subunit. {ECO:0000250};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Temperature dependence:
CC Thermostable. Retains about 45% of its activity after treatment of 90
CC degrees Celsius for 30 minutes. {ECO:0000269|PubMed:3149972};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:3149972}.
CC -!- INDUCTION: Is expressed in the stationary phase. Up-regulated by NprA.
CC {ECO:0000269|PubMed:2203733}.
CC -!- SIMILARITY: Belongs to the peptidase M4 family. {ECO:0000305}.
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DR EMBL; M21663; AAB02774.1; -; Genomic_DNA.
DR EMBL; M34237; AAA22625.1; -; Genomic_DNA.
DR PIR; A46564; A46564.
DR PIR; B36706; B36706.
DR PDB; 5DLH; X-ray; 2.25 A; A=236-551.
DR PDB; 5ONP; X-ray; 1.34 A; A=236-551.
DR PDB; 5ONQ; X-ray; 1.17 A; A=236-551.
DR PDB; 5WR2; X-ray; 2.00 A; A=236-551.
DR PDB; 5WR3; X-ray; 2.10 A; A=236-551.
DR PDB; 5WR4; X-ray; 2.10 A; A=236-551.
DR PDB; 5WR5; X-ray; 1.90 A; A=236-551.
DR PDB; 5WR6; X-ray; 2.30 A; A=236-551.
DR PDB; 6FHP; X-ray; 1.70 A; C/D=490-551.
DR PDB; 6FSM; X-ray; 1.39 A; A=236-551.
DR PDB; 6GHX; X-ray; 1.16 A; A=236-551.
DR PDB; 6Y4I; X-ray; 1.16 A; E=236-551.
DR PDB; 6YI6; X-ray; 1.44 A; E=236-551.
DR PDB; 6YMR; X-ray; 1.60 A; E=236-551.
DR PDB; 6YMS; X-ray; 1.32 A; E=236-551.
DR PDBsum; 5DLH; -.
DR PDBsum; 5ONP; -.
DR PDBsum; 5ONQ; -.
DR PDBsum; 5WR2; -.
DR PDBsum; 5WR3; -.
DR PDBsum; 5WR4; -.
DR PDBsum; 5WR5; -.
DR PDBsum; 5WR6; -.
DR PDBsum; 6FHP; -.
DR PDBsum; 6FSM; -.
DR PDBsum; 6GHX; -.
DR PDBsum; 6Y4I; -.
DR PDBsum; 6YI6; -.
DR PDBsum; 6YMR; -.
DR PDBsum; 6YMS; -.
DR AlphaFoldDB; P43133; -.
DR BMRB; P43133; -.
DR SMR; P43133; -.
DR ChEMBL; CHEMBL4523227; -.
DR DrugBank; DB01935; 3-{[(1r)-1-Benzyl-2-Sulfanylethyl]Amino}-3-Oxopropanoic Acid.
DR DrugBank; DB02597; [2(R,S)-2-Sulfanylheptanoyl]-Phe-Ala.
DR DrugBank; DB04569; Benzyl formate.
DR DrugBank; DB01786; D-Alanine.
DR DrugBank; DB02655; D-Aspartic Acid.
DR DrugBank; DB02517; D-Glutamic Acid.
DR DrugBank; DB03700; D-Threonine.
DR DrugBank; DB03308; L-Leucyl-Hydroxylamine.
DR DrugBank; DB03949; N-[(2S)-3-Phenyl-2-sulfanylpropanoyl]-L-phenylalanyl-L-tyrosine.
DR DrugBank; DB02669; RB106.
DR MEROPS; M04.001; -.
DR PRIDE; P43133; -.
DR BRENDA; 3.4.24.28; 623.
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 Gene3D; 1.10.390.10; -; 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 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 PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Direct protein sequencing; Hydrolase; Metal-binding;
KW Metalloprotease; Protease; Secreted; Signal; Zinc; Zymogen.
FT SIGNAL 1..31
FT /evidence="ECO:0000255"
FT PROPEP 32..235
FT /note="Activation peptide"
FT /evidence="ECO:0000269|PubMed:2203733,
FT ECO:0000269|PubMed:3149972"
FT /id="PRO_0000028612"
FT CHAIN 236..551
FT /note="Thermolysin"
FT /id="PRO_0000028613"
FT ACT_SITE 378
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT ACT_SITE 466
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 292
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 294
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 296
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 373
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 377
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 381
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 401
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 412
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 412
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 418
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
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 422
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 425
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 425
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 429
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 432
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 435
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT CONFLICT 10..14
FT /note="VRFGL -> RSFGV (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 24
FT /note="Missing (in Ref. 2; AAB02774)"
FT /evidence="ECO:0000305"
FT CONFLICT 29..33
FT /note="ALAST -> RLASS (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 114
FT /note="A -> Q (in Ref. 2; AAB02774)"
FT /evidence="ECO:0000305"
FT CONFLICT 124
FT /note="T -> S (in Ref. 2; AAB02774)"
FT /evidence="ECO:0000305"
FT CONFLICT 134
FT /note="P -> PIP (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 261
FT /note="T -> S (in Ref. 2; AAB02774)"
FT /evidence="ECO:0000305"
FT CONFLICT 463
FT /note="G -> A (in Ref. 2; AAB02774)"
FT /evidence="ECO:0000305"
FT STRAND 239..246
FT /evidence="ECO:0007829|PDB:6GHX"
FT STRAND 252..267
FT /evidence="ECO:0007829|PDB:6GHX"
FT STRAND 274..278
FT /evidence="ECO:0007829|PDB:6GHX"
FT STRAND 282..286
FT /evidence="ECO:0007829|PDB:6GHX"
FT STRAND 291..297
FT /evidence="ECO:0007829|PDB:6GHX"
FT HELIX 300..302
FT /evidence="ECO:0007829|PDB:6GHX"
FT HELIX 303..323
FT /evidence="ECO:0007829|PDB:6GHX"
FT TURN 327..329
FT /evidence="ECO:0007829|PDB:6Y4I"
FT STRAND 335..344
FT /evidence="ECO:0007829|PDB:6GHX"
FT STRAND 348..350
FT /evidence="ECO:0007829|PDB:6GHX"
FT STRAND 355..358
FT /evidence="ECO:0007829|PDB:6GHX"
FT STRAND 362..366
FT /evidence="ECO:0007829|PDB:6GHX"
FT HELIX 368..370
FT /evidence="ECO:0007829|PDB:6GHX"
FT HELIX 372..386
FT /evidence="ECO:0007829|PDB:6GHX"
FT HELIX 394..415
FT /evidence="ECO:0007829|PDB:6GHX"
FT STRAND 421..424
FT /evidence="ECO:0007829|PDB:6GHX"
FT TURN 425..427
FT /evidence="ECO:0007829|PDB:6GHX"
FT STRAND 432..434
FT /evidence="ECO:0007829|PDB:6FSM"
FT STRAND 437..441
FT /evidence="ECO:0007829|PDB:6GHX"
FT HELIX 443..446
FT /evidence="ECO:0007829|PDB:6GHX"
FT HELIX 452..454
FT /evidence="ECO:0007829|PDB:6GHX"
FT HELIX 460..464
FT /evidence="ECO:0007829|PDB:6GHX"
FT TURN 465..468
FT /evidence="ECO:0007829|PDB:6GHX"
FT HELIX 469..481
FT /evidence="ECO:0007829|PDB:6GHX"
FT STRAND 483..485
FT /evidence="ECO:0007829|PDB:6GHX"
FT STRAND 488..490
FT /evidence="ECO:0007829|PDB:6GHX"
FT HELIX 495..508
FT /evidence="ECO:0007829|PDB:6GHX"
FT HELIX 516..531
FT /evidence="ECO:0007829|PDB:6GHX"
FT HELIX 536..547
FT /evidence="ECO:0007829|PDB:6GHX"
SQ SEQUENCE 551 AA; 60617 MW; FCF4B2B5A7870129 CRC64;
MKRKMKMKLV RFGLAAGLAA QVFFLPYNAL ASTEHVTWNQ QFQTPQFISG DLLKVNGTSP
EELVYQYVEK NENKFKFHEN AKDTLQLKEK KNDNLGFTFM RFQQTYKGIP VFGAVVTAHV
KDGTLTALSG TLIPNLDTKG SLKSGKKLSE KQARDIAEKD LVANVTKEVP EYEQGKDTEF
VVYVNGDEAS LAYVVNLNFL TPEPGNWLYI IDAVDGKILN KFNQLDAAKP GDVKSITGTS
TVGVGRGVLG DQKNINTTYS TYYYLQDNTR GNGIFTYDAK YRTTLPGSLW ADADNQFFAS
YDAPAVDAHY YAGVTYDYYK NVHNRLSYDG NNAAIRSSVH YSQGYNNAFW NGSQMVYGDG
DGQTFIPLSG GIDVVAHELT HAVTDYTAGL IYQNESGAIN EAISDIFGTL VEFYANKNPD
WEIGEDVYTP GISGDSLRSM SDPAKYGDPD HYSKRYTGTQ DNGGVHINSG IINKAAYLIS
QGGTHYGVSV VGIGRDKLGK IFYRALTQYL TPTSNFSQLR AAAVQSATDL YGSTSQEVAS
VKQAFDAVGV K
