GGT_BACNA
ID GGT_BACNA Reviewed; 587 AA.
AC P63186;
DT 27-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 27-SEP-2004, sequence version 1.
DT 03-AUG-2022, entry version 70.
DE RecName: Full=Glutathione hydrolase proenzyme;
DE EC=3.4.19.13;
DE AltName: Full=Gamma-glutamyltranspeptidase proenzyme {ECO:0000303|PubMed:1371053};
DE Short=Gamma-GTP {ECO:0000303|PubMed:1371053};
DE EC=2.3.2.2 {ECO:0000269|PubMed:1371053};
DE Contains:
DE RecName: Full=Glutathione hydrolase large chain;
DE Contains:
DE RecName: Full=Glutathione hydrolase small chain;
DE Flags: Precursor;
GN Name=ggt;
OS Bacillus subtilis subsp. natto.
OC Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae; Bacillus.
OX NCBI_TaxID=86029;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND POSSIBLE INDUCTION.
RC STRAIN=NR-1;
RX PubMed=9339568; DOI=10.1271/bbb.61.1596;
RA Ogawa Y., Sugiura D., Motai H., Yuasa K., Tahara Y.;
RT "DNA sequence of Bacillus subtilis (natto) NR-1 gamma-
RT glutamyltranspeptidase gene, ggt.";
RL Biosci. Biotechnol. Biochem. 61:1596-1600(1997).
RN [2]
RP PROTEIN SEQUENCE OF 36-52 AND 403-442, FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND SUBCELLULAR LOCATION.
RC STRAIN=NR-1;
RX PubMed=1371053; DOI=10.1271/bbb1961.55.2971;
RA Ogawa Y., Hosoyama H., Hamano M., Motai H.;
RT "Purification and properties of gamma-glutamyltranspeptidase from Bacillus
RT subtilis (natto).";
RL Agric. Biol. Chem. 55:2971-2977(1991).
CC -!- FUNCTION: Cleaves the gamma-glutamyl bond of extracellular glutathione
CC (gamma-Glu-Cys-Gly), glutathione conjugates, and other gamma-glutamyl
CC compounds. The metabolism of glutathione releases free glutamate and
CC the dipeptide cysteinyl-glycine, which is hydrolyzed to cysteine and
CC glycine by dipeptidases. Uses glutamine as a gamma-glutamyl donor and
CC acceptor for gamma-polyglutamic acid synthesis. Dipeptides are better
CC gamma-glutamyl acceptors than free amino acids (PubMed:1371053).
CC {ECO:0000269|PubMed:1371053}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an alpha-amino acid + an N-terminal (5-L-glutamyl)-[peptide] =
CC 5-L-glutamyl amino acid + N-terminal L-alpha-aminoacyl-[peptide];
CC Xref=Rhea:RHEA:23904, Rhea:RHEA-COMP:9780, Rhea:RHEA-COMP:9795,
CC ChEBI:CHEBI:77644, ChEBI:CHEBI:78597, ChEBI:CHEBI:78599,
CC ChEBI:CHEBI:78608; EC=2.3.2.2; Evidence={ECO:0000269|PubMed:1371053};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glutathione + H2O = L-cysteinylglycine + L-glutamate;
CC Xref=Rhea:RHEA:28807, ChEBI:CHEBI:15377, ChEBI:CHEBI:29985,
CC ChEBI:CHEBI:57925, ChEBI:CHEBI:61694; EC=3.4.19.13;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an S-substituted glutathione + H2O = an S-substituted L-
CC cysteinylglycine + L-glutamate; Xref=Rhea:RHEA:59468,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:29985, ChEBI:CHEBI:90779,
CC ChEBI:CHEBI:143103; EC=3.4.19.13;
CC -!- ACTIVITY REGULATION: Inhibited by glucose.
CC {ECO:0000305|PubMed:9339568}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 8.0-8.5 for transfer of p-nitroanilide from gamma-
CC glutamyl-p-nitroanilide (gamma-GpNA) to glycylglycine (gly-gly).
CC {ECO:0000269|PubMed:1371053};
CC Temperature dependence:
CC Optimum temperature is 60 degrees Celsius.
CC {ECO:0000269|PubMed:1371053};
CC -!- PATHWAY: Sulfur metabolism; glutathione metabolism.
CC -!- SUBUNIT: This enzyme consists of two polypeptide chains, which are
CC synthesized in precursor form from a single polypeptide.
CC {ECO:0000269|PubMed:1371053}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1371053}.
CC -!- PTM: Cleaved by autocatalysis into a large and small subunit.
CC {ECO:0000269|PubMed:1371053}.
CC -!- SIMILARITY: Belongs to the gamma-glutamyltransferase family.
CC {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 PIR; F69631; F69631.
DR AlphaFoldDB; P63186; -.
DR SMR; P63186; -.
DR UniPathway; UPA00204; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0036374; F:glutathione hydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0102953; F:hypoglycin A gamma-glutamyl transpeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0103068; F:leukotriene C4 gamma-glutamyl transferase activity; IEA:UniProtKB-EC.
DR GO; GO:0006750; P:glutathione biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0006751; P:glutathione catabolic process; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 1.10.246.130; -; 1.
DR Gene3D; 3.60.20.40; -; 1.
DR InterPro; IPR043138; GGT_lsub_C.
DR InterPro; IPR000101; GGT_peptidase.
DR InterPro; IPR043137; GGT_ssub.
DR InterPro; IPR029055; Ntn_hydrolases_N.
DR SUPFAM; SSF56235; SSF56235; 1.
DR TIGRFAMs; TIGR00066; g_glut_trans; 1.
DR PROSITE; PS00462; G_GLU_TRANSPEPTIDASE; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Direct protein sequencing; Glutathione biosynthesis;
KW Hydrolase; Protease; Secreted; Signal; Transferase; Zymogen.
FT SIGNAL 1..28
FT /evidence="ECO:0000255"
FT PROPEP 29..35
FT /evidence="ECO:0000255"
FT /id="PRO_0000011046"
FT CHAIN 36..402
FT /note="Glutathione hydrolase large chain"
FT /id="PRO_0000011047"
FT CHAIN 403..587
FT /note="Glutathione hydrolase small chain"
FT /id="PRO_0000011048"
FT ACT_SITE 403
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P54422"
FT BINDING 113
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:P54422"
FT BINDING 421
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250"
FT BINDING 423
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:P54422"
FT BINDING 442
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:P54422"
FT BINDING 445
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:P54422"
FT BINDING 464..465
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:P54422"
FT BINDING 485..486
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:P54422"
FT CONFLICT 46
FT /note="D -> V (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 587 AA; 64070 MW; 4025FB5FC9A33C58 CRC64;
MKRTWNVCLT ALLSVLLVAG SVPFHAEAKK PPKSYDEYKQ VDVGKDGMVA TAHALASEIG
ADVLKKGGNA IDAAVAIQFA LNVTEPMMSG IGGGGFMMVY DGKTKDTTII DSRERAPAGA
TPDMFLDENG KAIPFSERVT KGTAVGVPGT LKGLEEALDK WGTRSMKLLI TLTIKLAEKG
FPIDSVLADA ISDYQEKLSR TAAKDVFLPN GEPLKEGDTL IQKDLAKTFK LIRSKGTDAF
YKGKFAKTLS DTVQDFGGSM TEKDLENYDI TIDEPIWGDY QGYQIATTPP PSSGGIFLLQ
MLKILDDFNL SQYDVRSWEK YQLLAETMHL SYADRASYAG DPEFVNVPLK GLLHPDYIKE
RQQLINLDQV NKKPKAGDPW KYQEGSANYK QVEQPKDKVE GQTTHFTVAD RWGNVVSYTT
TIEQLFGTGI MVPDYGVILN NELTDFDAIP GGANEVQPNK RPLSSMTPTI LFKDDKPVLT
VGSPGGATII SSVLQTILYH IEYGMGLKAA VEEPRIYTTS MSSYRYEDGV PKDVLSKLNG
MGHRFGTSPV DIGNVQSISI DHENGTFKGV VISGSNDAAI GINLKRK
