ID   AMPX_VIBPR              Reviewed;         504 AA.
AC   Q01693;
DT   01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1993, sequence version 1.
DT   03-MAY-2023, entry version 125.
DE   RecName: Full=Bacterial leucyl aminopeptidase;
DE            EC=3.4.11.10;
DE   Flags: Precursor;
OS   Vibrio proteolyticus (Aeromonas proteolytica).
OC   Bacteria; Pseudomonadota; Gammaproteobacteria; Vibrionales; Vibrionaceae;
OC   Vibrio.
OX   NCBI_TaxID=671;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 107-136 AND 233-405,
RP   AND PROTEOLYTIC PROCESSING.
RC   STRAIN=ATCC 15338 / DSM 30189 / CCUG 20302 / JCM 21193 / LMG 3772 /
RC   NBRC 13287 / NCIMB 1326;
RX   PubMed=1627651; DOI=10.1016/0167-4781(92)90037-z;
RA   van Heeke G., Denslow S., Watkins J., Wilson K., Wagner F.;
RT   "Cloning and nucleotide sequence of the Vibrio proteolyticus aminopeptidase
RT   gene.";
RL   Biochim. Biophys. Acta 1131:337-340(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 73-504, SUBCELLULAR LOCATION, AND
RP   PROTEOLYTIC PROCESSING.
RX   PubMed=1569090; DOI=10.1016/s0021-9258(18)42457-x;
RA   Guenet C., Lepage P., Harris B.A.;
RT   "Isolation of the leucine aminopeptidase gene from Aeromonas proteolytica.
RT   Evidence for an enzyme precursor.";
RL   J. Biol. Chem. 267:8390-8395(1992).
RN   [3]
RP   CRYSTALLIZATION.
RX   PubMed=1550363; DOI=10.1016/0003-9861(92)90141-i;
RA   Schalk C., Remy J.M., Chevrier B., Moras D., Tarnus C.;
RT   "Rapid purification of the Aeromonas proteolytica aminopeptidase:
RT   crystallization and preliminary X-ray data.";
RL   Arch. Biochem. Biophys. 294:91-97(1992).
RN   [4]
RP   X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 107-397 IN COMPLEX WITH ZINC.
RX   PubMed=8087555; DOI=10.1016/s0969-2126(00)00030-7;
RA   Chevrier B., Schalk C., D'Orchymont H., Rondeau J.-M., Moras D., Tarnus C.;
RT   "Crystal structure of Aeromonas proteolytica aminopeptidase: a prototypical
RT   member of the co-catalytic zinc enzyme family.";
RL   Structure 2:283-290(1994).
RN   [5]
RP   X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 107-397 IN COMPLEX WITH ZINC AND
RP   INHIBITOR.
RX   PubMed=8647077; DOI=10.1111/j.1432-1033.1996.0393k.x;
RA   Chevrier B., D'Orchymont H., Schalk C., Tarnus C., Moras D.;
RT   "The structure of the Aeromonas proteolytica aminopeptidase complexed with
RT   a hydroxamate inhibitor. Involvement in catalysis of Glu151 and two zinc
RT   ions of the co-catalytic unit.";
RL   Eur. J. Biochem. 237:393-398(1996).
RN   [6]
RP   X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 107-397 IN COMPLEX WITH ZINC AND
RP   INHIBITOR.
RX   PubMed=10413478; DOI=10.1021/bi9900572;
RA   De Paola C.C., Bennett B., Holz R.C., Ringe D., Petsko G.A.;
RT   "1-butaneboronic acid binding to Aeromonas proteolytica aminopeptidase: a
RT   case of arrested development.";
RL   Biochemistry 38:9048-9053(1999).
RN   [7]
RP   X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 107-397 IN COMPLEX WITH ZINC AND
RP   INHIBITOR.
RX   PubMed=11401547; DOI=10.1021/bi0100891;
RA   Stamper C., Bennett B., Edwards T., Holz R.C., Ringe D., Petsko G.A.;
RT   "Inhibition of the aminopeptidase from Aeromonas proteolytica by L-
RT   leucinephosphonic acid. Spectroscopic and crystallographic characterization
RT   of the transition state of peptide hydrolysis.";
RL   Biochemistry 40:7035-7046(2001).
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Release of an N-terminal amino acid, preferentially leucine,
CC         but not glutamic or aspartic acids.; EC=3.4.11.10;
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000269|PubMed:10413478, ECO:0000269|PubMed:11401547,
CC         ECO:0000269|PubMed:8087555, ECO:0000269|PubMed:8647077};
CC       Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000269|PubMed:10413478,
CC       ECO:0000269|PubMed:11401547, ECO:0000269|PubMed:8087555,
CC       ECO:0000269|PubMed:8647077};
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1569090}.
CC   -!- SIMILARITY: Belongs to the peptidase M28 family. M28E subfamily.
CC       {ECO:0000305}.
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DR   EMBL; Z11993; CAA78039.1; -; Genomic_DNA.
DR   EMBL; M85159; AAA21940.1; -; Genomic_DNA.
DR   PIR; S24314; S24314.
DR   PDB; 1AMP; X-ray; 1.80 A; A=107-397.
DR   PDB; 1CP6; X-ray; 1.90 A; A=107-397.
DR   PDB; 1FT7; X-ray; 2.20 A; A=107-397.
DR   PDB; 1IGB; X-ray; 2.30 A; A=107-397.
DR   PDB; 1LOK; X-ray; 1.20 A; A=107-397.
DR   PDB; 1RTQ; X-ray; 0.95 A; A=107-405.
DR   PDB; 1TXR; X-ray; 2.00 A; A=107-405.
DR   PDB; 1XRY; X-ray; 2.10 A; A=107-405.
DR   PDB; 2ANP; X-ray; 1.90 A; A=107-397.
DR   PDB; 2DEA; X-ray; 1.24 A; A=107-405.
DR   PDB; 2IQ6; X-ray; 2.00 A; A=107-397.
DR   PDB; 2NYQ; X-ray; 2.50 A; A=107-405.
DR   PDB; 2PRQ; X-ray; 2.15 A; A=107-397.
DR   PDB; 3B35; X-ray; 1.10 A; A=107-397.
DR   PDB; 3B3C; X-ray; 1.46 A; A=107-397.
DR   PDB; 3B3S; X-ray; 1.18 A; A=107-397.
DR   PDB; 3B3T; X-ray; 1.17 A; A=107-397.
DR   PDB; 3B3V; X-ray; 1.22 A; A=107-397.
DR   PDB; 3B3W; X-ray; 1.75 A; A=107-397.
DR   PDB; 3B7I; X-ray; 1.75 A; A=107-397.
DR   PDB; 3FH4; X-ray; 1.95 A; A=107-405.
DR   PDB; 3VH9; X-ray; 1.29 A; A=107-405.
DR   PDBsum; 1AMP; -.
DR   PDBsum; 1CP6; -.
DR   PDBsum; 1FT7; -.
DR   PDBsum; 1IGB; -.
DR   PDBsum; 1LOK; -.
DR   PDBsum; 1RTQ; -.
DR   PDBsum; 1TXR; -.
DR   PDBsum; 1XRY; -.
DR   PDBsum; 2ANP; -.
DR   PDBsum; 2DEA; -.
DR   PDBsum; 2IQ6; -.
DR   PDBsum; 2NYQ; -.
DR   PDBsum; 2PRQ; -.
DR   PDBsum; 3B35; -.
DR   PDBsum; 3B3C; -.
DR   PDBsum; 3B3S; -.
DR   PDBsum; 3B3T; -.
DR   PDBsum; 3B3V; -.
DR   PDBsum; 3B3W; -.
DR   PDBsum; 3B7I; -.
DR   PDBsum; 3FH4; -.
DR   PDBsum; 3VH9; -.
DR   AlphaFoldDB; Q01693; -.
DR   SMR; Q01693; -.
DR   BindingDB; Q01693; -.
DR   ChEMBL; CHEMBL3750; -.
DR   DrugBank; DB02664; 1-Butane Boronic Acid.
DR   DrugBank; DB02386; Leucine Phosphonic Acid.
DR   DrugBank; DB01980; Para-Iodo-D-Phenylalanine Hydroxamic Acid.
DR   DrugBank; DB03424; Ubenimex.
DR   DrugCentral; Q01693; -.
DR   MEROPS; M28.002; -.
DR   BRENDA; 3.4.11.10; 167.
DR   SABIO-RK; Q01693; -.
DR   EvolutionaryTrace; Q01693; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0004177; F:aminopeptidase activity; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0008235; F:metalloexopeptidase activity; IEA:InterPro.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   CDD; cd03879; M28_AAP; 1.
DR   Gene3D; 2.60.120.380; -; 1.
DR   Gene3D; 3.40.630.10; Zn peptidases; 1.
DR   InterPro; IPR045175; M28_fam.
DR   InterPro; IPR012189; Pept_M28E_Ap1.
DR   InterPro; IPR007280; Peptidase_C_arc/bac.
DR   InterPro; IPR007484; Peptidase_M28.
DR   PANTHER; PTHR12147:SF26; ENDOPLASMIC RETICULUM METALLOPEPTIDASE 1; 1.
DR   PANTHER; PTHR12147; METALLOPEPTIDASE M28 FAMILY MEMBER; 1.
DR   Pfam; PF04389; Peptidase_M28; 1.
DR   Pfam; PF04151; PPC; 1.
DR   PIRSF; PIRSF036685; BacLeuNPeptidase; 1.
DR   SUPFAM; SSF89260; Collagen-binding domain; 1.
DR   SUPFAM; SSF53187; Zn-dependent exopeptidases; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Aminopeptidase; Direct protein sequencing; Disulfide bond;
KW   Hydrolase; Metal-binding; Protease; Secreted; Signal; Zinc; Zymogen.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000255"
FT   PROPEP          22..106
FT                   /evidence="ECO:0000269|PubMed:1569090,
FT                   ECO:0000269|PubMed:1627651"
FT                   /id="PRO_0000026849"
FT   CHAIN           107..405
FT                   /note="Bacterial leucyl aminopeptidase"
FT                   /id="PRO_0000026850"
FT   PROPEP          406..504
FT                   /note="Removed in mature form"
FT                   /evidence="ECO:0000269|PubMed:1627651"
FT                   /id="PRO_0000026851"
FT   BINDING         203
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:10413478,
FT                   ECO:0000269|PubMed:11401547, ECO:0000269|PubMed:8087555,
FT                   ECO:0000269|PubMed:8647077, ECO:0007744|PDB:1AMP,
FT                   ECO:0007744|PDB:1CP6, ECO:0007744|PDB:1FT7,
FT                   ECO:0007744|PDB:1IGB, ECO:0007744|PDB:1LOK,
FT                   ECO:0007744|PDB:1RTQ, ECO:0007744|PDB:1TXR,
FT                   ECO:0007744|PDB:1XRY, ECO:0007744|PDB:2ANP,
FT                   ECO:0007744|PDB:2DEA, ECO:0007744|PDB:2IQ6,
FT                   ECO:0007744|PDB:2NYQ, ECO:0007744|PDB:3B35,
FT                   ECO:0007744|PDB:3B3C, ECO:0007744|PDB:3B3S,
FT                   ECO:0007744|PDB:3B3T, ECO:0007744|PDB:3B3V,
FT                   ECO:0007744|PDB:3B3W, ECO:0007744|PDB:3B7I,
FT                   ECO:0007744|PDB:3FH4, ECO:0007744|PDB:3VH9"
FT   BINDING         223
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:10413478,
FT                   ECO:0000269|PubMed:11401547, ECO:0000269|PubMed:8087555,
FT                   ECO:0000269|PubMed:8647077, ECO:0007744|PDB:1AMP,
FT                   ECO:0007744|PDB:1CP6, ECO:0007744|PDB:1FT7,
FT                   ECO:0007744|PDB:1IGB, ECO:0007744|PDB:1LOK,
FT                   ECO:0007744|PDB:1RTQ, ECO:0007744|PDB:1TXR,
FT                   ECO:0007744|PDB:1XRY, ECO:0007744|PDB:2ANP,
FT                   ECO:0007744|PDB:2DEA, ECO:0007744|PDB:2IQ6,
FT                   ECO:0007744|PDB:2NYQ, ECO:0007744|PDB:3B35,
FT                   ECO:0007744|PDB:3B3C, ECO:0007744|PDB:3B3S,
FT                   ECO:0007744|PDB:3B3T, ECO:0007744|PDB:3B3V,
FT                   ECO:0007744|PDB:3B3W, ECO:0007744|PDB:3B7I,
FT                   ECO:0007744|PDB:3FH4, ECO:0007744|PDB:3VH9"
FT   BINDING         223
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000269|PubMed:10413478,
FT                   ECO:0000269|PubMed:11401547, ECO:0000269|PubMed:8087555,
FT                   ECO:0000269|PubMed:8647077, ECO:0007744|PDB:1AMP,
FT                   ECO:0007744|PDB:1CP6, ECO:0007744|PDB:1FT7,
FT                   ECO:0007744|PDB:1IGB, ECO:0007744|PDB:1LOK,
FT                   ECO:0007744|PDB:1RTQ, ECO:0007744|PDB:1TXR,
FT                   ECO:0007744|PDB:1XRY, ECO:0007744|PDB:2ANP,
FT                   ECO:0007744|PDB:2DEA, ECO:0007744|PDB:2IQ6,
FT                   ECO:0007744|PDB:2NYQ, ECO:0007744|PDB:3B35,
FT                   ECO:0007744|PDB:3B3C, ECO:0007744|PDB:3B3S,
FT                   ECO:0007744|PDB:3B3T, ECO:0007744|PDB:3B3V,
FT                   ECO:0007744|PDB:3B3W, ECO:0007744|PDB:3B7I,
FT                   ECO:0007744|PDB:3FH4, ECO:0007744|PDB:3VH9"
FT   BINDING         258
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000269|PubMed:10413478,
FT                   ECO:0000269|PubMed:11401547, ECO:0000269|PubMed:8087555,
FT                   ECO:0000269|PubMed:8647077, ECO:0007744|PDB:1AMP,
FT                   ECO:0007744|PDB:1CP6, ECO:0007744|PDB:1FT7,
FT                   ECO:0007744|PDB:1IGB, ECO:0007744|PDB:1LOK,
FT                   ECO:0007744|PDB:1RTQ, ECO:0007744|PDB:1TXR,
FT                   ECO:0007744|PDB:1XRY, ECO:0007744|PDB:2ANP,
FT                   ECO:0007744|PDB:2DEA, ECO:0007744|PDB:2IQ6,
FT                   ECO:0007744|PDB:2NYQ, ECO:0007744|PDB:3B35,
FT                   ECO:0007744|PDB:3B3C, ECO:0007744|PDB:3B3S,
FT                   ECO:0007744|PDB:3B3T, ECO:0007744|PDB:3B3V,
FT                   ECO:0007744|PDB:3B3W, ECO:0007744|PDB:3B7I,
FT                   ECO:0007744|PDB:3FH4, ECO:0007744|PDB:3VH9"
FT   BINDING         285
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:10413478,
FT                   ECO:0000269|PubMed:11401547, ECO:0000269|PubMed:8087555,
FT                   ECO:0000269|PubMed:8647077, ECO:0007744|PDB:1AMP,
FT                   ECO:0007744|PDB:1CP6, ECO:0007744|PDB:1FT7,
FT                   ECO:0007744|PDB:1IGB, ECO:0007744|PDB:1LOK,
FT                   ECO:0007744|PDB:1RTQ, ECO:0007744|PDB:1TXR,
FT                   ECO:0007744|PDB:1XRY, ECO:0007744|PDB:2ANP,
FT                   ECO:0007744|PDB:2DEA, ECO:0007744|PDB:2IQ6,
FT                   ECO:0007744|PDB:2NYQ, ECO:0007744|PDB:3B35,
FT                   ECO:0007744|PDB:3B3C, ECO:0007744|PDB:3B3S,
FT                   ECO:0007744|PDB:3B3T, ECO:0007744|PDB:3B3V,
FT                   ECO:0007744|PDB:3B3W, ECO:0007744|PDB:3B7I,
FT                   ECO:0007744|PDB:3FH4, ECO:0007744|PDB:3VH9"
FT   BINDING         362
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000269|PubMed:10413478,
FT                   ECO:0000269|PubMed:11401547, ECO:0000269|PubMed:8087555,
FT                   ECO:0000269|PubMed:8647077, ECO:0007744|PDB:1AMP,
FT                   ECO:0007744|PDB:1CP6, ECO:0007744|PDB:1FT7,
FT                   ECO:0007744|PDB:1IGB, ECO:0007744|PDB:1LOK,
FT                   ECO:0007744|PDB:1RTQ, ECO:0007744|PDB:1TXR,
FT                   ECO:0007744|PDB:1XRY, ECO:0007744|PDB:2ANP,
FT                   ECO:0007744|PDB:2DEA, ECO:0007744|PDB:2IQ6,
FT                   ECO:0007744|PDB:2NYQ, ECO:0007744|PDB:3B35,
FT                   ECO:0007744|PDB:3B3C, ECO:0007744|PDB:3B3S,
FT                   ECO:0007744|PDB:3B3T, ECO:0007744|PDB:3B3V,
FT                   ECO:0007744|PDB:3B3W, ECO:0007744|PDB:3B7I,
FT                   ECO:0007744|PDB:3FH4, ECO:0007744|PDB:3VH9"
FT   DISULFID        329..333
FT                   /evidence="ECO:0000269|PubMed:10413478,
FT                   ECO:0000269|PubMed:11401547, ECO:0000269|PubMed:8087555,
FT                   ECO:0000269|PubMed:8647077, ECO:0007744|PDB:1AMP,
FT                   ECO:0007744|PDB:1CP6, ECO:0007744|PDB:1FT7,
FT                   ECO:0007744|PDB:1IGB"
FT   CONFLICT        303..304
FT                   /note="TD -> DT (in Ref. 1; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        306
FT                   /note="N -> D (in Ref. 1; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        312..314
FT                   /note="TQL -> QT (in Ref. 1; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   HELIX           113..119
FT                   /evidence="ECO:0007829|PDB:1RTQ"
FT   HELIX           120..122
FT                   /evidence="ECO:0007829|PDB:1RTQ"
FT   HELIX           125..136
FT                   /evidence="ECO:0007829|PDB:1RTQ"
FT   HELIX           146..163
FT                   /evidence="ECO:0007829|PDB:1RTQ"
FT   STRAND          164..166
FT                   /evidence="ECO:0007829|PDB:2NYQ"
FT   STRAND          169..176
FT                   /evidence="ECO:0007829|PDB:1RTQ"
FT   STRAND          179..188
FT                   /evidence="ECO:0007829|PDB:1RTQ"
FT   STRAND          191..203
FT                   /evidence="ECO:0007829|PDB:1RTQ"
FT   TURN            221..224
FT                   /evidence="ECO:0007829|PDB:1RTQ"
FT   HELIX           225..240
FT                   /evidence="ECO:0007829|PDB:1RTQ"
FT   STRAND          246..255
FT                   /evidence="ECO:0007829|PDB:1RTQ"
FT   HELIX           257..259
FT                   /evidence="ECO:0007829|PDB:1RTQ"
FT   HELIX           262..273
FT                   /evidence="ECO:0007829|PDB:1RTQ"
FT   STRAND          277..283
FT                   /evidence="ECO:0007829|PDB:1RTQ"
FT   STRAND          292..299
FT                   /evidence="ECO:0007829|PDB:1RTQ"
FT   STRAND          301..303
FT                   /evidence="ECO:0007829|PDB:3B3T"
FT   HELIX           305..318
FT                   /evidence="ECO:0007829|PDB:1RTQ"
FT   STRAND          324..327
FT                   /evidence="ECO:0007829|PDB:1RTQ"
FT   HELIX           336..341
FT                   /evidence="ECO:0007829|PDB:1RTQ"
FT   STRAND          349..352
FT                   /evidence="ECO:0007829|PDB:1RTQ"
FT   HELIX           354..356
FT                   /evidence="ECO:0007829|PDB:1RTQ"
FT   TURN            359..362
FT                   /evidence="ECO:0007829|PDB:1RTQ"
FT   HELIX           368..370
FT                   /evidence="ECO:0007829|PDB:1RTQ"
FT   HELIX           376..394
FT                   /evidence="ECO:0007829|PDB:1RTQ"
SQ   SEQUENCE   504 AA;  54232 MW;  7B33317EF6153B48 CRC64;
     MKYTKTLLAM VLSATFCQAY AEDKVWISIG ADANQTVMKS GAESILPNSV ASSGQVWVGQ
     VDVAQLAELS HNMHEEHNRC GGYMVHPSAQ SAMAASAMPT TLASFVMPPI TQQATVTAWL
     PQVDASQITG TISSLESFTN RFYTTTSGAQ ASDWIASEWQ ALSASLPNAS VKQVSHSGYN
     QKSVVMTITG SEAPDEWIVI GGHLDSTIGS HTNEQSVAPG ADDDASGIAA VTEVIRVLSE
     NNFQPKRSIA FMAYAAEEVG LRGSQDLANQ YKSEGKNVVS ALQLDMTNYK GSAQDVVFIT
     DYTDSNFTQY LTQLMDEYLP SLTYGFDTCG YACSDHASWH NAGYPAAMPF ESKFNDYNPR
     IHTTQDTLAN SDPTGSHAKK FTQLGLAYAI EMGSATGDTP TPGNQLEDGV PVTDLSGSRG
     SNVWYTFELE TQKNLQITTS GGYGDLDLYV KFGSKASKQN WDCRPYLSGN NEVCTFNNAS
     PGTYSVMLTG YSNYSGASLK ASTF
//