CBPG_PSES6
ID CBPG_PSES6 Reviewed; 415 AA.
AC P06621;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1988, sequence version 1.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=Carboxypeptidase G2;
DE Short=CPDG2;
DE EC=3.4.17.11;
DE AltName: Full=Folate hydrolase G2;
DE AltName: Full=Glutamate carboxypeptidase;
DE AltName: Full=Pteroylmonoglutamic acid hydrolase G2;
DE AltName: INN=Glucarpidase;
DE Flags: Precursor;
GN Name=cpg2;
OS Pseudomonas sp. (strain RS-16).
OC Bacteria; Proteobacteria.
OX NCBI_TaxID=312;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=6396165; DOI=10.1016/0378-1119(84)90192-6;
RA Minton N.P., Atkinson T., Bruton C.J., Sherwood R.F.;
RT "The complete nucleotide sequence of the Pseudomonas gene coding for
RT carboxypeptidase G2.";
RL Gene 31:31-38(1984).
RN [2]
RP ERRATUM OF PUBMED:6396165.
RA Minton N.P., Atkinson T., Bruton C.J., Sherwood R.F.;
RL Gene 42:353-353(1986).
RN [3]
RP CHARACTERIZATION.
RX PubMed=3838935; DOI=10.1111/j.1432-1033.1985.tb08860.x;
RA Sherwood R.F., Melton R.G., Alwan S.M., Hughes P.;
RT "Purification and properties of carboxypeptidase G2 from Pseudomonas sp.
RT strain RS-16. Use of a novel triazine dye affinity method.";
RL Eur. J. Biochem. 148:447-453(1985).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 23-415 IN COMPLEX WITH ZINC,
RP COFACTOR, AND ACTIVE SITE.
RX PubMed=9083113; DOI=10.1016/s0969-2126(97)00191-3;
RA Rowsell S., Pauptit R.A., Tucker A.D., Melton R.G., Blow D.M., Brick P.;
RT "Crystal structure of carboxypeptidase G2, a bacterial enzyme with
RT applications in cancer therapy.";
RL Structure 5:337-347(1997).
CC -!- FUNCTION: Catalyzes the hydrolysis of reduced and non-reduced folates
CC to pteroates and L-glutamate. This enzyme has a broad specificity.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of C-terminal glutamate residues from a wide range of
CC N-acylating moieties, including peptidyl, aminoacyl, benzoyl,
CC benzyloxycarbonyl, folyl and pteroyl groups.; EC=3.4.17.11;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:9083113};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000269|PubMed:9083113};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:9083113}.
CC -!- PHARMACEUTICAL: Used clinically as a folate-depleting, antitumor agent.
CC -!- SIMILARITY: Belongs to the peptidase M20A family. {ECO:0000305}.
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DR EMBL; M12599; AAA62842.1; -; Genomic_DNA.
DR PIR; A24955; YXPSF2.
DR PDB; 1CG2; X-ray; 2.50 A; A/B/C/D=23-415.
DR PDB; 6XJ5; X-ray; 3.11 A; A/B/C/D/E/F/G/H=24-415.
DR PDB; 7M6U; X-ray; 2.59 A; A/B/C/D=25-415.
DR PDBsum; 1CG2; -.
DR PDBsum; 6XJ5; -.
DR PDBsum; 7M6U; -.
DR AlphaFoldDB; P06621; -.
DR SASBDB; P06621; -.
DR SMR; P06621; -.
DR MEROPS; M20.001; -.
DR BRENDA; 3.4.17.11; 5085.
DR SABIO-RK; P06621; -.
DR EvolutionaryTrace; P06621; -.
DR GO; GO:0004180; F:carboxypeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008237; F:metallopeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR InterPro; IPR001261; ArgE/DapE_CS.
DR InterPro; IPR036264; Bact_exopeptidase_dim_dom.
DR InterPro; IPR017150; Pept_M20_glutamate_carboxypep.
DR InterPro; IPR002933; Peptidase_M20.
DR InterPro; IPR011650; Peptidase_M20_dimer.
DR Pfam; PF07687; M20_dimer; 1.
DR Pfam; PF01546; Peptidase_M20; 1.
DR PIRSF; PIRSF037238; Carboxypeptidase_G2; 1.
DR SUPFAM; SSF55031; SSF55031; 1.
DR PROSITE; PS00758; ARGE_DAPE_CPG2_1; 1.
DR PROSITE; PS00759; ARGE_DAPE_CPG2_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Carboxypeptidase; Direct protein sequencing; Hydrolase;
KW Metal-binding; Metalloprotease; Pharmaceutical; Protease; Signal; Zinc.
FT SIGNAL 1..22
FT CHAIN 23..415
FT /note="Carboxypeptidase G2"
FT /id="PRO_0000026808"
FT ACT_SITE 114
FT /evidence="ECO:0000250"
FT ACT_SITE 175
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:9083113"
FT BINDING 112
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:9083113"
FT BINDING 141
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:9083113"
FT BINDING 141
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:9083113"
FT BINDING 176
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:9083113"
FT BINDING 200
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:9083113"
FT BINDING 385
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:9083113"
FT HELIX 30..51
FT /evidence="ECO:0007829|PDB:1CG2"
FT HELIX 60..76
FT /evidence="ECO:0007829|PDB:1CG2"
FT STRAND 80..85
FT /evidence="ECO:0007829|PDB:1CG2"
FT STRAND 92..100
FT /evidence="ECO:0007829|PDB:1CG2"
FT STRAND 107..112
FT /evidence="ECO:0007829|PDB:1CG2"
FT HELIX 121..124
FT /evidence="ECO:0007829|PDB:1CG2"
FT STRAND 128..130
FT /evidence="ECO:0007829|PDB:1CG2"
FT STRAND 133..135
FT /evidence="ECO:0007829|PDB:1CG2"
FT TURN 137..142
FT /evidence="ECO:0007829|PDB:1CG2"
FT HELIX 143..158
FT /evidence="ECO:0007829|PDB:1CG2"
FT STRAND 164..173
FT /evidence="ECO:0007829|PDB:1CG2"
FT HELIX 175..177
FT /evidence="ECO:0007829|PDB:1CG2"
FT TURN 178..182
FT /evidence="ECO:0007829|PDB:1CG2"
FT HELIX 183..192
FT /evidence="ECO:0007829|PDB:1CG2"
FT STRAND 194..198
FT /evidence="ECO:0007829|PDB:1CG2"
FT STRAND 208..213
FT /evidence="ECO:0007829|PDB:1CG2"
FT STRAND 215..224
FT /evidence="ECO:0007829|PDB:1CG2"
FT STRAND 230..232
FT /evidence="ECO:0007829|PDB:6XJ5"
FT HELIX 234..236
FT /evidence="ECO:0007829|PDB:1CG2"
FT HELIX 240..251
FT /evidence="ECO:0007829|PDB:1CG2"
FT HELIX 252..254
FT /evidence="ECO:0007829|PDB:1CG2"
FT TURN 257..260
FT /evidence="ECO:0007829|PDB:1CG2"
FT STRAND 261..270
FT /evidence="ECO:0007829|PDB:1CG2"
FT STRAND 279..291
FT /evidence="ECO:0007829|PDB:1CG2"
FT HELIX 292..306
FT /evidence="ECO:0007829|PDB:1CG2"
FT STRAND 315..322
FT /evidence="ECO:0007829|PDB:1CG2"
FT HELIX 330..346
FT /evidence="ECO:0007829|PDB:1CG2"
FT STRAND 352..355
FT /evidence="ECO:0007829|PDB:1CG2"
FT STRAND 356..358
FT /evidence="ECO:0007829|PDB:6XJ5"
FT HELIX 363..366
FT /evidence="ECO:0007829|PDB:1CG2"
FT HELIX 367..369
FT /evidence="ECO:0007829|PDB:1CG2"
FT STRAND 380..382
FT /evidence="ECO:0007829|PDB:1CG2"
FT STRAND 386..388
FT /evidence="ECO:0007829|PDB:1CG2"
FT STRAND 391..393
FT /evidence="ECO:0007829|PDB:1CG2"
FT HELIX 394..396
FT /evidence="ECO:0007829|PDB:1CG2"
FT HELIX 397..412
FT /evidence="ECO:0007829|PDB:1CG2"
SQ SEQUENCE 415 AA; 43932 MW; 8483A52202CE9C5E CRC64;
MRPSIHRTAI AAVLATAFVA GTALAQKRDN VLFQAATDEQ PAVIKTLEKL VNIETGTGDA
EGIAAAGNFL EAELKNLGFT VTRSKSAGLV VGDNIVGKIK GRGGKNLLLM SHMDTVYLKG
ILAKAPFRVE GDKAYGPGIA DDKGGNAVIL HTLKLLKEYG VRDYGTITVL FNTDEEKGSF
GSRDLIQEEA KLADYVLSFE PTSAGDEKLS LGTSGIAYVQ VNITGKASHA GAAPELGVNA
LVEASDLVLR TMNIDDKAKN LRFNWTIAKA GNVSNIIPAS ATLNADVRYA RNEDFDAAMK
TLEERAQQKK LPEADVKVIV TRGRPAFNAG EGGKKLVDKA VAYYKEAGGT LGVEERTGGG
TDAAYAALSG KPVIESLGLP GFGYHSDKAE YVDISAIPRR LYMAARLIMD LGAGK
