CBPA1_BOVIN
ID CBPA1_BOVIN Reviewed; 419 AA.
AC P00730;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1991, sequence version 3.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Carboxypeptidase A1 {ECO:0000305};
DE EC=3.4.17.1 {ECO:0000250|UniProtKB:P15085};
DE Flags: Precursor;
GN Name=CPA1; Synonyms=CPA;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Pancreas;
RX PubMed=1998496; DOI=10.1016/s0006-291x(05)81207-0;
RA le Hueerou I., Guilloteau P., Toullec R., Puigserver A., Wicker C.;
RT "Cloning and nucleotide sequence of a bovine pancreatic
RT preprocarboxypeptidase A cDNA.";
RL Biochem. Biophys. Res. Commun. 175:110-116(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Pancreas;
RX PubMed=8522204; DOI=10.1016/0378-1119(95)00454-e;
RA Goo J.H., Kim K.H., Choi K.Y.;
RT "Cloning, sequencing and expression of the gene encoding a major allotypic
RT preprocarboxypeptidase A from bovine pancreas.";
RL Gene 165:333-334(1995).
RN [3]
RP PROTEIN SEQUENCE OF 111-417.
RX PubMed=5102489; DOI=10.1021/bi00782a004;
RA Bradshaw R.A., Walsh K.A., Neurath H.;
RT "Amino acid sequence of bovine carboxypeptidase A. Tryptic and chymotryptic
RT peptides of the cyanogen bromide fragment F-I.";
RL Biochemistry 10:938-950(1971).
RN [4]
RP SEQUENCE REVISION TO 138 AND 141.
RX PubMed=5143102; DOI=10.1021/bi00798a600;
RA Petra P.H., Hermodson M.A., Walsh K.A., Neurath H.;
RT "Characterization of bovine carboxypeptidase A (Allan).";
RL Biochemistry 10:4023-4025(1971).
RN [5]
RP PROTEIN SEQUENCE OF 17-120.
RX PubMed=3147705; DOI=10.1016/0300-9084(88)90178-2;
RA Wade R.D., Hass G.M., Kumar S., Walsh K.A., Neurath H.;
RT "The amino acid sequence of the activation peptide of bovine pro-
RT carboxypeptidase A.";
RL Biochimie 70:1137-1142(1988).
RN [6]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=12729612; DOI=10.1016/s0003-9861(03)00080-8;
RA Reddanna P., Prabhu K.S., Whelan J., Reddy C.C.;
RT "Carboxypeptidase A-catalyzed direct conversion of leukotriene C4 to
RT leukotriene F4.";
RL Arch. Biochem. Biophys. 413:158-163(2003).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.54 ANGSTROMS).
RX PubMed=6887246; DOI=10.1016/s0022-2836(83)80024-2;
RA Rees D.C., Lewis M., Lipscomb W.N.;
RT "Refined crystal structure of carboxypeptidase A at 1.54-A resolution.";
RL J. Mol. Biol. 168:367-387(1983).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 111-417 IN COMPLEX WITH ZINC IONS
RP AND SUBSTRATE ANALOG.
RX PubMed=15299490; DOI=10.1107/s0907444993007267;
RA Teplyakov A., Wilson K.S., Orioli P., Mangani S.;
RT "High-resolution structure of the complex between carboxypeptidase A and L-
RT phenyl lactate.";
RL Acta Crystallogr. D 49:534-540(1993).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF COMPLEX WITH CPA1 AND CTRC, AND
RP TISSUE SPECIFICITY.
RX PubMed=7556081; DOI=10.1002/j.1460-2075.1995.tb00117.x;
RA Gomis-Rueth F.-X., Gomez M., Bode W., Huber R., Aviles F.X.;
RT "The three-dimensional structure of the native ternary complex of bovine
RT pancreatic procarboxypeptidase A with proproteinase E and chymotrypsinogen
RT C.";
RL EMBO J. 14:4387-4394(1995).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 111-419 OF APOENZYME AND IN
RP COMPLEX WITH ZINC IONS.
RX PubMed=9867434; DOI=10.1107/s0907444997010445;
RA Greenblatt H.M., Feinberg H., Tucker P.A., Shoham G.;
RT "Carboxypeptidase A: native, zinc-removed and mercury-replaced forms.";
RL Acta Crystallogr. D 54:289-305(1998).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 111-417 IN COMPLEX WITH ZINC IONS
RP AND INHIBITOR.
RX PubMed=10955996; DOI=10.1021/bi000952h;
RA van Aalten D.M.F., Chong C.R., Joshua-Tor L.;
RT "Crystal structure of carboxypeptidase A complexed with D-cysteine at 1.75
RT A -- inhibitor-induced conformational changes.";
RL Biochemistry 39:10082-10089(2000).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 111-417 IN COMPLEX WITH ZINC IONS
RP AND SUBSTRATE ANALOG.
RX PubMed=11937361; DOI=10.1016/s0968-0896(01)00429-1;
RA Cho J.H., Kim D.H., Chung S.J., Ha N.-C., Oh B.-H., Yong Choi K.;
RT "Insight into the stereochemistry in the inhibition of carboxypeptidase A
RT with N-(hydroxyaminocarbonyl)phenylalanine: binding modes of an
RT enantiomeric pair of the inhibitor to carboxypeptidase A.";
RL Bioorg. Med. Chem. 10:2015-2022(2002).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 111-417 IN COMPLEX WITH ZINC IONS
RP AND SUBSTRATE ANALOG.
RX PubMed=12431056; DOI=10.1021/jm020258v;
RA Park J.D., Kim D.H., Kim S.-J., Woo J.-R., Ryu S.E.;
RT "Sulfamide-based inhibitors for carboxypeptidase A. Novel type transition
RT state analogue inhibitors for zinc proteases.";
RL J. Med. Chem. 45:5295-5302(2002).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) OF 111-417 IN COMPLEX WITH ZINC
RP IONS.
RX PubMed=12554943; DOI=10.1107/s0907444902015706;
RA Kilshtain-Vardi A., Glick M., Greenblatt H.M., Goldblum A., Shoham G.;
RT "Refined structure of bovine carboxypeptidase A at 1.25 A resolution.";
RL Acta Crystallogr. D 59:323-333(2003).
RN [15]
RP VARIANTS ALLELIC VAL-289; ALA-338 AND VAL-415.
RX PubMed=5817619; DOI=10.1021/bi00835a011;
RA Petra P.H., Bradshaw R.A., Walsh K.A., Neurath H.;
RT "Identification of the amino acid replacements characterizing the allotypic
RT forms of bovine carboxypeptidase A.";
RL Biochemistry 8:2762-2768(1969).
CC -!- FUNCTION: Carboxypeptidase that catalyzes the release of a C-terminal
CC amino acid, but has little or no action with -Asp, -Glu, -Arg, -Lys or
CC -Pro (By similarity). Catalyzes the conversion of leukotriene C4 to
CC leukotriene F4 via the hydrolysis of an amide bond (PubMed:12729612).
CC {ECO:0000250|UniProtKB:P15085, ECO:0000269|PubMed:12729612}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of a C-terminal amino acid, but little or no action
CC with -Asp, -Glu, -Arg, -Lys or -Pro.; EC=3.4.17.1;
CC Evidence={ECO:0000250|UniProtKB:P15085};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + leukotriene C4 = glycine + leukotriene F4;
CC Xref=Rhea:RHEA:50740, ChEBI:CHEBI:15377, ChEBI:CHEBI:57305,
CC ChEBI:CHEBI:57973, ChEBI:CHEBI:133618;
CC Evidence={ECO:0000269|PubMed:12729612};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50741;
CC Evidence={ECO:0000269|PubMed:12729612};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P15085};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:P15085};
CC -!- SUBUNIT: Monomer. May form a complex with proelastase 2.
CC {ECO:0000250|UniProtKB:P15085}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P15085}.
CC -!- TISSUE SPECIFICITY: Pancreas. {ECO:0000269|PubMed:7556081}.
CC -!- SIMILARITY: Belongs to the peptidase M14 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Worthington enzyme manual;
CC URL="https://www.worthington-biochem.com/COA/";
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DR EMBL; M61851; AAA30426.1; -; mRNA.
DR EMBL; Z33906; CAA83955.1; -; mRNA.
DR PIR; JN0126; CPBOA.
DR RefSeq; NP_777175.1; NM_174750.2.
DR PDB; 1ARL; X-ray; 1.88 A; A=111-417.
DR PDB; 1ARM; X-ray; 1.76 A; A=111-419.
DR PDB; 1BAV; X-ray; 1.60 A; A/B/C/D=111-419.
DR PDB; 1CBX; X-ray; 2.00 A; A=111-417.
DR PDB; 1CPS; X-ray; 2.25 A; A=111-417.
DR PDB; 1CPX; X-ray; 2.00 A; A=111-417.
DR PDB; 1EE3; X-ray; 1.70 A; P=111-419.
DR PDB; 1ELL; X-ray; 1.76 A; P=111-419.
DR PDB; 1ELM; X-ray; 2.00 A; P=111-419.
DR PDB; 1F57; X-ray; 1.75 A; A=111-417.
DR PDB; 1HDQ; X-ray; 2.30 A; A=111-417.
DR PDB; 1HDU; X-ray; 1.75 A; A/B/D/E=111-414.
DR PDB; 1HEE; X-ray; 1.75 A; A/B/D/E=111-414.
DR PDB; 1IY7; X-ray; 2.00 A; A=111-417.
DR PDB; 1M4L; X-ray; 1.25 A; A=111-417.
DR PDB; 1PYT; X-ray; 2.35 A; A=17-110, B=111-419.
DR PDB; 1YME; X-ray; 1.53 A; A=111-419.
DR PDB; 1ZLH; X-ray; 1.70 A; A=111-419.
DR PDB; 2ABZ; X-ray; 2.16 A; A/B=111-419.
DR PDB; 2CTB; X-ray; 1.50 A; A=111-417.
DR PDB; 2CTC; X-ray; 1.40 A; A=111-417.
DR PDB; 2RFH; X-ray; 1.70 A; A=111-417.
DR PDB; 3CPA; X-ray; 2.00 A; A=111-417.
DR PDB; 3FVL; X-ray; 1.85 A; A/C/E=111-417.
DR PDB; 3FX6; X-ray; 1.85 A; A/C/E=111-417.
DR PDB; 3I1U; X-ray; 1.39 A; A=111-419.
DR PDB; 3KGQ; X-ray; 1.70 A; A=111-419.
DR PDB; 4CPA; X-ray; 2.50 A; A/B=111-417.
DR PDB; 5CPA; X-ray; 1.54 A; A=111-417.
DR PDB; 6CPA; X-ray; 2.00 A; A=111-417.
DR PDB; 7CPA; X-ray; 2.00 A; A=111-417.
DR PDB; 8CPA; X-ray; 2.00 A; A=111-417.
DR PDBsum; 1ARL; -.
DR PDBsum; 1ARM; -.
DR PDBsum; 1BAV; -.
DR PDBsum; 1CBX; -.
DR PDBsum; 1CPS; -.
DR PDBsum; 1CPX; -.
DR PDBsum; 1EE3; -.
DR PDBsum; 1ELL; -.
DR PDBsum; 1ELM; -.
DR PDBsum; 1F57; -.
DR PDBsum; 1HDQ; -.
DR PDBsum; 1HDU; -.
DR PDBsum; 1HEE; -.
DR PDBsum; 1IY7; -.
DR PDBsum; 1M4L; -.
DR PDBsum; 1PYT; -.
DR PDBsum; 1YME; -.
DR PDBsum; 1ZLH; -.
DR PDBsum; 2ABZ; -.
DR PDBsum; 2CTB; -.
DR PDBsum; 2CTC; -.
DR PDBsum; 2RFH; -.
DR PDBsum; 3CPA; -.
DR PDBsum; 3FVL; -.
DR PDBsum; 3FX6; -.
DR PDBsum; 3I1U; -.
DR PDBsum; 3KGQ; -.
DR PDBsum; 4CPA; -.
DR PDBsum; 5CPA; -.
DR PDBsum; 6CPA; -.
DR PDBsum; 7CPA; -.
DR PDBsum; 8CPA; -.
DR AlphaFoldDB; P00730; -.
DR PCDDB; P00730; -.
DR SMR; P00730; -.
DR DIP; DIP-44716N; -.
DR IntAct; P00730; 1.
DR MINT; P00730; -.
DR STRING; 9913.ENSBTAP00000009745; -.
DR BindingDB; P00730; -.
DR ChEMBL; CHEMBL3481; -.
DR SwissLipids; SLP:000001634; -.
DR MEROPS; M14.001; -.
DR PaxDb; P00730; -.
DR GeneID; 286762; -.
DR KEGG; bta:286762; -.
DR CTD; 1357; -.
DR eggNOG; KOG2650; Eukaryota.
DR InParanoid; P00730; -.
DR OrthoDB; 524270at2759; -.
DR BRENDA; 3.4.17.1; 908.
DR SABIO-RK; P00730; -.
DR EvolutionaryTrace; P00730; -.
DR PRO; PR:P00730; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0004181; F:metallocarboxypeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006691; P:leukotriene metabolic process; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd03870; M14_CPA; 1.
DR Gene3D; 3.30.70.340; -; 1.
DR InterPro; IPR034248; CPA_M14_CPD.
DR InterPro; IPR036990; M14A-like_propep.
DR InterPro; IPR003146; M14A_act_pep.
DR InterPro; IPR000834; Peptidase_M14.
DR Pfam; PF00246; Peptidase_M14; 1.
DR Pfam; PF02244; Propep_M14; 1.
DR PRINTS; PR00765; CRBOXYPTASEA.
DR SMART; SM00631; Zn_pept; 1.
DR PROSITE; PS00132; CARBOXYPEPT_ZN_1; 1.
DR PROSITE; PS00133; CARBOXYPEPT_ZN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Carboxypeptidase; Direct protein sequencing; Disulfide bond;
KW Hydrolase; Metal-binding; Metalloprotease; Protease; Reference proteome;
KW Secreted; Signal; Zinc; Zymogen.
FT SIGNAL 1..16
FT /evidence="ECO:0000269|PubMed:3147705"
FT PROPEP 17..110
FT /note="Activation peptide"
FT /evidence="ECO:0000269|PubMed:5102489"
FT /id="PRO_0000004343"
FT CHAIN 111..419
FT /note="Carboxypeptidase A1"
FT /id="PRO_0000004344"
FT ACT_SITE 380
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:P00732"
FT BINDING 179..182
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:12431056,
FT ECO:0007744|PDB:1IY7"
FT BINDING 179
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:12431056,
FT ECO:0007744|PDB:1IY7"
FT BINDING 182
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:12431056,
FT ECO:0007744|PDB:1IY7"
FT BINDING 237
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:12431056,
FT ECO:0007744|PDB:1IY7"
FT BINDING 254..255
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:12431056,
FT ECO:0007744|PDB:1IY7"
FT BINDING 306
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:12431056,
FT ECO:0007744|PDB:1IY7"
FT BINDING 307..308
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:12431056,
FT ECO:0007744|PDB:1IY7"
FT BINDING 358
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:12431056,
FT ECO:0007744|PDB:1IY7"
FT DISULFID 248..271
FT /evidence="ECO:0000250|UniProtKB:P15085"
FT VARIANT 289
FT /note="I -> V (in allelic variant)"
FT /evidence="ECO:0000269|PubMed:5817619"
FT VARIANT 338
FT /note="E -> A (in allelic variant)"
FT /evidence="ECO:0000269|PubMed:5817619"
FT VARIANT 415
FT /note="L -> V (in allelic variant)"
FT /evidence="ECO:0000269|PubMed:5817619"
FT CONFLICT 95
FT /note="S -> L (in Ref. 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 199
FT /note="D -> N (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 203
FT /note="D -> N (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 224
FT /note="D -> N (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 232
FT /note="Q -> E (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 295
FT /note="D -> N (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 24..29
FT /evidence="ECO:0007829|PDB:1PYT"
FT HELIX 33..40
FT /evidence="ECO:0007829|PDB:1PYT"
FT TURN 41..43
FT /evidence="ECO:0007829|PDB:1PYT"
FT HELIX 46..48
FT /evidence="ECO:0007829|PDB:1PYT"
FT STRAND 51..54
FT /evidence="ECO:0007829|PDB:1PYT"
FT STRAND 63..67
FT /evidence="ECO:0007829|PDB:1PYT"
FT HELIX 69..81
FT /evidence="ECO:0007829|PDB:1PYT"
FT STRAND 85..91
FT /evidence="ECO:0007829|PDB:1PYT"
FT HELIX 93..106
FT /evidence="ECO:0007829|PDB:1PYT"
FT TURN 114..116
FT /evidence="ECO:0007829|PDB:1M4L"
FT STRAND 119..121
FT /evidence="ECO:0007829|PDB:1BAV"
FT HELIX 125..138
FT /evidence="ECO:0007829|PDB:1M4L"
FT TURN 140..142
FT /evidence="ECO:0007829|PDB:1M4L"
FT STRAND 143..150
FT /evidence="ECO:0007829|PDB:1M4L"
FT STRAND 156..162
FT /evidence="ECO:0007829|PDB:1M4L"
FT STRAND 164..168
FT /evidence="ECO:0007829|PDB:3FVL"
FT STRAND 171..176
FT /evidence="ECO:0007829|PDB:1M4L"
FT HELIX 183..199
FT /evidence="ECO:0007829|PDB:1M4L"
FT TURN 200..202
FT /evidence="ECO:0007829|PDB:1M4L"
FT HELIX 204..212
FT /evidence="ECO:0007829|PDB:1M4L"
FT STRAND 214..219
FT /evidence="ECO:0007829|PDB:1M4L"
FT HELIX 223..231
FT /evidence="ECO:0007829|PDB:1M4L"
FT STRAND 244..247
FT /evidence="ECO:0007829|PDB:1BAV"
FT HELIX 253..255
FT /evidence="ECO:0007829|PDB:1M4L"
FT STRAND 257..260
FT /evidence="ECO:0007829|PDB:1M4L"
FT STRAND 263..267
FT /evidence="ECO:0007829|PDB:1M4L"
FT STRAND 273..275
FT /evidence="ECO:0007829|PDB:4CPA"
FT HELIX 284..296
FT /evidence="ECO:0007829|PDB:1M4L"
FT STRAND 299..306
FT /evidence="ECO:0007829|PDB:1M4L"
FT STRAND 311..315
FT /evidence="ECO:0007829|PDB:1M4L"
FT HELIX 326..341
FT /evidence="ECO:0007829|PDB:1M4L"
FT TURN 342..344
FT /evidence="ECO:0007829|PDB:1M4L"
FT STRAND 349..352
FT /evidence="ECO:0007829|PDB:1M4L"
FT HELIX 353..356
FT /evidence="ECO:0007829|PDB:1M4L"
FT HELIX 364..370
FT /evidence="ECO:0007829|PDB:1M4L"
FT STRAND 375..380
FT /evidence="ECO:0007829|PDB:1M4L"
FT STRAND 384..387
FT /evidence="ECO:0007829|PDB:1M4L"
FT HELIX 388..390
FT /evidence="ECO:0007829|PDB:3I1U"
FT HELIX 393..395
FT /evidence="ECO:0007829|PDB:1M4L"
FT HELIX 396..416
FT /evidence="ECO:0007829|PDB:1M4L"
SQ SEQUENCE 419 AA; 47082 MW; 21B86407B3BFC452 CRC64;
MQGLLILSVL LGAALGKEDF VGHQVLRITA ADEAEVQTVK ELEDLEHLQL DFWRGPGQPG
SPIDVRVPFP SLQAVKVFLE AHGIRYRIMI EDVQSLLDEE QEQMFASQSR ARSTNTFNYA
TYHTLDEIYD FMDLLVAEHP QLVSKLQIGR SYEGRPIYVL KFSTGGSNRP AIWIDLGIHS
REWITQATGV WFAKKFTEDY GQDPSFTAIL DSMDIFLEIV TNPDGFAFTH SQNRLWRKTR
SVTSSSLCVG VDANRNWDAG FGKAGASSSP CSETYHGKYA NSEVEVKSIV DFVKDHGNFK
AFLSIHSYSQ LLLYPYGYTT QSIPDKTELN QVAKSAVEAL KSLYGTSYKY GSIITTIYQA
SGGSIDWSYN QGIKYSFTFE LRDTGRYGFL LPASQIIPTA QETWLGVLTI MEHTLNNLY
