ID   PEPO_LACLS              Reviewed;         627 AA.
AC   Q02VB0; Q09145;
DT   09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   03-AUG-2022, entry version 78.
DE   RecName: Full=Neutral endopeptidase;
DE            EC=3.4.24.-;
DE   AltName: Full=Endopeptidase O;
GN   Name=pepO; OrderedLocusNames=LACR_D16;
OS   Lactococcus lactis subsp. cremoris (strain SK11).
OG   Plasmid pLACR4, and Plasmid pSK11L.
OC   Bacteria; Firmicutes; Bacilli; Lactobacillales; Streptococcaceae;
OC   Lactococcus; Lactococcus cremoris subsp. cremoris.
OX   NCBI_TaxID=272622;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=SK11; PLASMID=pLACR4;
RX   PubMed=17030793; DOI=10.1073/pnas.0607117103;
RA   Makarova K.S., Slesarev A., Wolf Y.I., Sorokin A., Mirkin B., Koonin E.V.,
RA   Pavlov A., Pavlova N., Karamychev V., Polouchine N., Shakhova V.,
RA   Grigoriev I., Lou Y., Rohksar D., Lucas S., Huang K., Goodstein D.M.,
RA   Hawkins T., Plengvidhya V., Welker D., Hughes J., Goh Y., Benson A.,
RA   Baldwin K., Lee J.-H., Diaz-Muniz I., Dosti B., Smeianov V., Wechter W.,
RA   Barabote R., Lorca G., Altermann E., Barrangou R., Ganesan B., Xie Y.,
RA   Rawsthorne H., Tamir D., Parker C., Breidt F., Broadbent J.R., Hutkins R.,
RA   O'Sullivan D., Steele J., Unlu G., Saier M.H. Jr., Klaenhammer T.,
RA   Richardson P., Kozyavkin S., Weimer B.C., Mills D.A.;
RT   "Comparative genomics of the lactic acid bacteria.";
RL   Proc. Natl. Acad. Sci. U.S.A. 103:15611-15616(2006).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-288.
RC   PLASMID=pSK11L;
RX   PubMed=8586224;
RA   Yu W., Gillies K., Kondo J.K., Broadbent J.R., McKay L.L.;
RT   "Plasmid-mediated oligopeptide transport system in lactococci.";
RL   Dev. Biol. Stand. 85:509-521(1995).
RN   [3]
RP   PROTEIN SEQUENCE OF 2-22, ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND
RP   SUBUNIT.
RX   PubMed=8012609; DOI=10.1099/00221287-140-4-923;
RA   Pritchard G.G., Freebairn A.D., Coolbear T.;
RT   "Purification and characterization of an endopeptidase from Lactococcus
RT   lactis subsp. cremoris SK11.";
RL   Microbiology 140:923-930(1994).
CC   -!- FUNCTION: Endopeptidase with broad substrate specificity for several
CC       oligopeptides.
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC       Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC   -!- ACTIVITY REGULATION: Strongly inhibited by 1,10-phenanthroline and
CC       phosphoramidon but relatively insensitive to EDTA. Not significantly
CC       inhibited by p-chloromercuribenzoate nor by phenylmethylsulfonyl
CC       fluoride. {ECO:0000269|PubMed:8012609}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       pH dependence:
CC         Optimum pH is 6.0-6.5.;
CC       Temperature dependence:
CC         Optimum temperature is 30-38 degrees Celsius.;
CC   -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:8012609}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:8012609}.
CC   -!- SIMILARITY: Belongs to the peptidase M13 family. {ECO:0000255|PROSITE-
CC       ProRule:PRU01233, ECO:0000305}.
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DR   EMBL; CP000429; ABJ74112.1; -; Genomic_DNA.
DR   EMBL; U09553; AAB00538.1; -; Unassigned_DNA.
DR   RefSeq; WP_011669109.1; NC_008506.1.
DR   AlphaFoldDB; Q02VB0; -.
DR   SMR; Q02VB0; -.
DR   MEROPS; M13.004; -.
DR   EnsemblBacteria; ABJ74112; ABJ74112; LACR_D16.
DR   KEGG; llc:LACR_D16; -.
DR   HOGENOM; CLU_006187_7_2_9; -.
DR   OMA; FGWAQVW; -.
DR   Proteomes; UP000000240; Plasmid pLACR4.
DR   GO; GO:0005737; C:cytoplasm; 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; cd08662; M13; 1.
DR   Gene3D; 1.10.1380.10; -; 1.
DR   Gene3D; 3.40.390.10; -; 1.
DR   InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR   InterPro; IPR000718; Peptidase_M13.
DR   InterPro; IPR018497; Peptidase_M13_C.
DR   InterPro; IPR042089; Peptidase_M13_dom_2.
DR   InterPro; IPR008753; Peptidase_M13_N.
DR   PANTHER; PTHR11733; PTHR11733; 1.
DR   Pfam; PF01431; Peptidase_M13; 1.
DR   Pfam; PF05649; Peptidase_M13_N; 1.
DR   PRINTS; PR00786; NEPRILYSIN.
DR   PROSITE; PS51885; NEPRILYSIN; 1.
DR   PROSITE; PS00142; ZINC_PROTEASE; 1.
PE   1: Evidence at protein level;
KW   Cytoplasm; Direct protein sequencing; Hydrolase; Metal-binding;
KW   Metalloprotease; Plasmid; Protease; Zinc.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000269|PubMed:8012609"
FT   CHAIN           2..627
FT                   /note="Neutral endopeptidase"
FT                   /id="PRO_0000272023"
FT   DOMAIN          1..627
FT                   /note="Peptidase M13"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT   ACT_SITE        476
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01233,
FT                   ECO:0000255|PROSITE-ProRule:PRU10095"
FT   ACT_SITE        539
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
FT   BINDING         475
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01233,
FT                   ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         479
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01233,
FT                   ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         535
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01233"
SQ   SEQUENCE   627 AA;  71528 MW;  916B70C7FE9A68D7 CRC64;
     MTRIQDDLFA TVNAEWLENA EIPADKPRIS AFDELVLKNE KNLAKDLADL SQNLPTDNPE
     LLEAIKFYNK AGDWQAREKA DFSAVKNELA KVETLNTFED FKNNLTQLVF HSQAPLPFSF
     SVEPDMKDAI HYSLGFSGPG LILPDTTYYN DEHPRKKELL DFWAKNTSEI LKTFDVENAE
     EIAKSALKFD ALLVPSANTS EEWAKYAELY HPISTDSFVS KVKNLDLKSL IKDLVKTEPD
     KVIVYEDRFY ESFDSLINEE NWSLIKAWML TKIARGATSF FNEDLRILGG AYGRFLSNVQ
     EARSQEKHQL DLTESYFSQV IGLFYGKKYF GEAGKADVKR MVTAMIKVYQ ARLSKNEWLS
     QETAEKAIEK LDAITPFIGF PDKLPEIYSR LKTTSGSLYE DALKFDEILT ARTFEKFSED
     VDKTSWHMPA HMVNAYYSPD SNTIVFPAAI LQAPFYSLEQ SSSQNYGGIG TVIAHEISHA
     FDNNGAQFDK EGNLNKWWLD EDYEAFEEKQ KEMIALFDGV ETEAGPANGK LIVSENIADQ
     GGITAALTAA KDEKDVDLKA FFSQWAKIWR MKASKEFQQM LLSMDFHAPA KLRANIPPTN
     LEEFYDTFDV KETDKMYRAP ENRLKIW