ID NPRE_BACCE Reviewed; 566 AA. AC P05806; DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1996, sequence version 2. DT 24-JAN-2024, entry version 152. DE RecName: Full=Bacillolysin; DE EC=3.4.24.28; DE AltName: Full=Neutral protease; DE Flags: Precursor; GN Name=npr; Synonyms=nprC; OS Bacillus cereus. OC Bacteria; Bacillota; Bacilli; Bacillales; Bacillaceae; Bacillus; OC Bacillus cereus group. OX NCBI_TaxID=1396; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=1495388; DOI=10.1111/j.1365-2958.1992.tb00884.x; RA Wetmore D.R., Wong S.L., Roche R.S.; RT "The role of the pro-sequence in the processing and secretion of the RT thermolysin-like neutral protease from Bacillus cereus."; RL Mol. Microbiol. 6:1593-1604(1992). RN [2] RP PROTEIN SEQUENCE OF 250-566. RC STRAIN=DSM 3101 / x-3; RX PubMed=3092843; DOI=10.1515/bchm3.1986.367.2.643; RA Sidler W., Niederer E., Suter F., Zuber H.; RT "The primary structure of Bacillus cereus neutral proteinase and comparison RT with thermolysin and Bacillus subtilis neutral proteinase."; RL Biol. Chem. Hoppe-Seyler 367:643-657(1986). RN [3] RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS). RX PubMed=3127592; DOI=10.1016/0022-2836(88)90623-7; RA Pauptit R.A., Karlsson R., Picot D., Jenkins J.A., Niklaus-Reimer A.-S., RA Jansonius J.N.; RT "Crystal structure of neutral protease from Bacillus cereus refined at 3.0- RT A resolution and comparison with the homologous but more thermostable RT enzyme thermolysin."; RL J. Mol. Biol. 199:525-537(1988). RN [4] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS). RX PubMed=1633827; DOI=10.1111/j.1432-1033.1992.tb17109.x; RA Stark W., Pauptit R.A., Wilson K.S., Jansonius J.N.; RT "The structure of neutral protease from Bacillus cereus at 0.2-nm RT resolution."; RL Eur. J. Biochem. 207:781-791(1992). RN [5] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF MUTANT SER-393. RX PubMed=15299677; DOI=10.1107/s0907444995016684; RA Lister S.A., Wetmore D.R., Roche R.S., Codding P.W.; RT "E144S active-site mutant of the Bacillus cereus thermolysin-like neutral RT protease at 2.8-A resolution."; RL Acta Crystallogr. D 52:543-550(1996). CC -!- FUNCTION: Extracellular zinc metalloprotease. CC -!- CATALYTIC ACTIVITY: CC Reaction=Similar, but not identical, to that of thermolysin.; CC EC=3.4.24.28; 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 Thermolabile.; 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; M83910; AAA22620.1; -; Genomic_DNA. DR PIR; S22690; HYBSU. DR RefSeq; WP_000730369.1; NZ_VSSM01000006.1. DR PDB; 1ESP; X-ray; 2.80 A; A=250-566. DR PDB; 1NPC; X-ray; 2.00 A; A=250-566. DR PDBsum; 1ESP; -. DR PDBsum; 1NPC; -. DR AlphaFoldDB; P05806; -. DR SMR; P05806; -. DR MEROPS; M04.001; -. DR PATRIC; fig|1396.444.peg.2749; -. DR eggNOG; COG3227; Bacteria. DR EvolutionaryTrace; P05806; -. 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 3D-structure; Calcium; Direct protein sequencing; Hydrolase; Metal-binding; KW Metalloprotease; Protease; Secreted; Signal; Zinc. FT SIGNAL 1..27 FT /evidence="ECO:0000255" FT PROPEP 28..249 FT /note="Activation peptide" FT /evidence="ECO:0000269|PubMed:3092843" FT /id="PRO_0000028598" FT CHAIN 250..566 FT /note="Bacillolysin" FT /id="PRO_0000028599" FT ACT_SITE 393 FT ACT_SITE 481 FT /note="Proton donor" FT BINDING 307 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:15299677" FT BINDING 309 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:15299677" FT BINDING 311 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT BINDING 388 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:15299677" FT BINDING 392 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:15299677" 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 ECO:0000269|PubMed:15299677" FT BINDING 416 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:15299677" FT BINDING 427 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:15299677" FT BINDING 427 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:15299677" FT BINDING 433 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT BINDING 435 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:15299677" FT BINDING 435 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:15299677" FT BINDING 437 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT BINDING 440 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:15299677" FT BINDING 440 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:15299677" FT BINDING 443 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT BINDING 444 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000269|PubMed:15299677" FT BINDING 447 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT BINDING 450 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000269|PubMed:15299677" FT STRAND 253..260 FT /evidence="ECO:0007829|PDB:1NPC" FT STRAND 266..274 FT /evidence="ECO:0007829|PDB:1NPC" FT STRAND 277..282 FT /evidence="ECO:0007829|PDB:1NPC" FT STRAND 284..287 FT /evidence="ECO:0007829|PDB:1NPC" FT STRAND 289..298 FT /evidence="ECO:0007829|PDB:1NPC" FT STRAND 306..312 FT /evidence="ECO:0007829|PDB:1NPC" FT HELIX 315..317 FT /evidence="ECO:0007829|PDB:1NPC" FT HELIX 318..338 FT /evidence="ECO:0007829|PDB:1NPC" FT TURN 342..345 FT /evidence="ECO:0007829|PDB:1NPC" FT STRAND 350..359 FT /evidence="ECO:0007829|PDB:1NPC" FT STRAND 363..365 FT /evidence="ECO:0007829|PDB:1NPC" FT STRAND 367..372 FT /evidence="ECO:0007829|PDB:1NPC" FT STRAND 377..380 FT /evidence="ECO:0007829|PDB:1NPC" FT HELIX 383..385 FT /evidence="ECO:0007829|PDB:1NPC" FT HELIX 387..400 FT /evidence="ECO:0007829|PDB:1NPC" FT TURN 401..403 FT /evidence="ECO:0007829|PDB:1NPC" FT HELIX 409..429 FT /evidence="ECO:0007829|PDB:1NPC" FT STRAND 436..439 FT /evidence="ECO:0007829|PDB:1NPC" FT TURN 440..442 FT /evidence="ECO:0007829|PDB:1NPC" FT STRAND 445..447 FT /evidence="ECO:0007829|PDB:1ESP" FT STRAND 452..456 FT /evidence="ECO:0007829|PDB:1NPC" FT HELIX 458..461 FT /evidence="ECO:0007829|PDB:1NPC" FT HELIX 467..469 FT /evidence="ECO:0007829|PDB:1NPC" FT HELIX 475..496 FT /evidence="ECO:0007829|PDB:1NPC" FT STRAND 498..500 FT /evidence="ECO:0007829|PDB:1NPC" FT STRAND 503..505 FT /evidence="ECO:0007829|PDB:1NPC" FT HELIX 510..523 FT /evidence="ECO:0007829|PDB:1NPC" FT HELIX 531..546 FT /evidence="ECO:0007829|PDB:1NPC" FT HELIX 551..562 FT /evidence="ECO:0007829|PDB:1NPC" SQ SEQUENCE 566 AA; 60919 MW; E18B4572C2C4E1D3 CRC64; MKKKSLALVL ATGMAVTTFG GTGSAFADSK NVLSTKKYNE TVQSPEFISG DLTEATGKKA ESVVFDYLNA AKGDYKLGEK SAQDSFKVKQ VKKDAVTDST VVRMQQVYEG VPVWGSTQVA HVSKDGSLKV LSGTVAPDLD KKEKLKNKNK IEGAKAIEIA QQDLGVTPKY EVEPKADLYV YQNGEETTYA YVVNLNFLDP SPGNYYYFIE ADSGKVLNKF NTIDHVTNDD KSPVKQEAPK QDAKAVVKPV TGTNKVGTGK GVLGDTKSLN TTLSGSSYYL QDNTRGATIF TYDAKNRSTL PGTLWADADN VFNAAYDAAA VDAHYYAGKT YDYYKATFNR NSINDAGAPL KSTVHYGSNY NNAFWNGSQM VYGDGDGVTF TSLSGGIDVI GHELTHAVTE NSSNLIYQNE SGALNEAISD IFGTLVEFYD NRNPDWEIGE DIYTPGKAGD ALRSMSDPTK YGDPDHYSKR YTGSSDNGGV HTNSGIINKQ AYLLANGGTH YGVTVTGIGK DKLGAIYYRA NTQYFTQSTT FSQARAGAVQ AAADLYGANS AEVAAVKQSF SAVGVN //