ID O25743_HELPY Unreviewed; 567 AA.
AC O25743;
DT 01-JAN-1998, integrated into UniProtKB/TrEMBL.
DT 01-JAN-1998, sequence version 1.
DT 27-MAR-2024, entry version 144.
DE RecName: Full=Glutathione hydrolase proenzyme {ECO:0000256|RuleBase:RU368036};
DE EC=2.3.2.2 {ECO:0000256|RuleBase:RU368036};
DE EC=3.4.19.13 {ECO:0000256|RuleBase:RU368036};
DE Contains:
DE RecName: Full=Glutathione hydrolase large chain {ECO:0000256|RuleBase:RU368036};
DE Contains:
DE RecName: Full=Glutathione hydrolase small chain {ECO:0000256|RuleBase:RU368036};
GN OrderedLocusNames=HP_1118 {ECO:0000313|EMBL:AAD08162.1};
OS Helicobacter pylori (strain ATCC 700392 / 26695) (Campylobacter pylori).
OC Bacteria; Campylobacterota; Epsilonproteobacteria; Campylobacterales;
OC Helicobacteraceae; Helicobacter.
OX NCBI_TaxID=85962 {ECO:0000313|EMBL:AAD08162.1, ECO:0000313|Proteomes:UP000000429};
RN [1] {ECO:0000313|EMBL:AAD08162.1, ECO:0000313|Proteomes:UP000000429}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700392 / 26695 {ECO:0000313|Proteomes:UP000000429};
RX PubMed=9252185; DOI=10.1038/41483;
RA Tomb J.-F., White O., Kerlavage A.R., Clayton R.A., Sutton G.G.,
RA Fleischmann R.D., Ketchum K.A., Klenk H.P., Gill S., Dougherty B.A.,
RA Nelson K., Quackenbush J., Zhou L., Kirkness E.F., Peterson S., Loftus B.,
RA Richardson D., Dodson R., Khalak H.G., Glodek A., McKenney K.,
RA Fitzegerald L.M., Lee N., Adams M.D., Hickey E.K., Berg D.E., Gocayne J.D.,
RA Utterback T.R., Peterson J.D., Kelley J.M., Karp P.D., Smith H.O.,
RA Fraser C.M., Venter J.C.;
RT "The complete genome sequence of the gastric pathogen Helicobacter
RT pylori.";
RL Nature 388:539-547(1997).
RN [2] {ECO:0007829|PDB:2QM6, ECO:0007829|PDB:2QMC}
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 25-379 AND 380-567 IN COMPLEX
RP WITH L-GLUTAMATE.
RX PubMed=17960917; DOI=10.1021/bi701599e;
RA Morrow A.L., Williams K., Sand A., Boanca G., Barycki J.J.;
RT "Characterization of Helicobacter pylori gamma-glutamyltranspeptidase
RT reveals the molecular basis for substrate specificity and a critical role
RT for the tyrosine 433-containing loop in catalysis.";
RL Biochemistry 46:13407-13414(2007).
RN [3] {ECO:0007829|PDB:2NQO}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 27-379 AND 380-567.
RX PubMed=17107958; DOI=10.1074/jbc.M607694200;
RA Boanca G., Sand A., Okada T., Suzuki H., Kumagai H., Fukuyama K.,
RA Barycki J.J.;
RT "Autoprocessing of Helicobacter pylori gamma-glutamyltranspeptidase leads
RT to the formation of a threonine-threonine catalytic dyad.";
RL J. Biol. Chem. 282:534-541(2007).
RN [4] {ECO:0007829|PDB:3FNM}
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 25-379 AND 380-567.
RX PubMed=19256527; DOI=10.1021/bi8014955;
RA Williams K., Cullati S., Sand A., Biterova E.I., Barycki J.J.;
RT "Crystal structure of acivicin-inhibited gamma-glutamyltranspeptidase
RT reveals critical roles for its C-terminus in autoprocessing and
RT catalysis.";
RL Biochemistry 48:2459-2467(2009).
RN [5] {ECO:0007829|PDB:5BPK}
RP X-RAY CRYSTALLOGRAPHY (1.49 ANGSTROMS) OF 1-379 AND 380-567.
RA Bolz C., Bach N.C., Meyer H., Mueller G., Dawidowski M., Popowicz G.,
RA Sieber S.A., Skerra A., Gerhard M.;
RT "Varying binding modes of inhibitors and structural differences in the
RT binding pockets of different gamma-glutamyltranspeptidases.";
RL Submitted (MAY-2015) to the PDB data bank.
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 Evidence={ECO:0000256|ARBA:ARBA00001049,
CC ECO:0000256|RuleBase:RU368036};
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;
CC Evidence={ECO:0000256|ARBA:ARBA00000250,
CC ECO:0000256|RuleBase:RU368036};
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 Evidence={ECO:0000256|ARBA:ARBA00001089,
CC ECO:0000256|RuleBase:RU368036};
CC -!- PATHWAY: Sulfur metabolism; glutathione metabolism.
CC {ECO:0000256|RuleBase:RU368036}.
CC -!- SUBUNIT: This enzyme consists of two polypeptide chains, which are
CC synthesized in precursor form from a single polypeptide.
CC {ECO:0000256|RuleBase:RU368036}.
CC -!- PTM: Cleaved by autocatalysis into a large and a small subunit.
CC {ECO:0000256|RuleBase:RU368036}.
CC -!- SIMILARITY: Belongs to the gamma-glutamyltransferase family.
CC {ECO:0000256|ARBA:ARBA00009381, ECO:0000256|RuleBase:RU368036}.
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 EMBL; AE000511; AAD08162.1; -; Genomic_DNA.
DR PIR; F64659; F64659.
DR RefSeq; NP_207909.1; NC_000915.1.
DR RefSeq; WP_001254471.1; NC_018939.1.
DR PDB; 2NQO; X-ray; 1.90 A; A/C=27-379, B/D=380-567.
DR PDB; 2QM6; X-ray; 1.60 A; A/C=25-379, B/D=380-567.
DR PDB; 2QMC; X-ray; 1.55 A; A/C=25-379, B/D=380-567.
DR PDB; 3FNM; X-ray; 1.70 A; A/C=25-379, B/D=380-567.
DR PDB; 5BPK; X-ray; 1.49 A; A/B=1-379, C/D=380-567.
DR PDBsum; 2NQO; -.
DR PDBsum; 2QM6; -.
DR PDBsum; 2QMC; -.
DR PDBsum; 3FNM; -.
DR PDBsum; 5BPK; -.
DR AlphaFoldDB; O25743; -.
DR SMR; O25743; -.
DR DIP; DIP-3652N; -.
DR IntAct; O25743; 11.
DR MINT; O25743; -.
DR STRING; 85962.HP_1118; -.
DR MEROPS; T03.001; -.
DR PaxDb; 85962-C694_05770; -.
DR EnsemblBacteria; AAD08162; AAD08162; HP_1118.
DR KEGG; hpy:HP_1118; -.
DR PATRIC; fig|85962.47.peg.1200; -.
DR eggNOG; COG0405; Bacteria.
DR InParanoid; O25743; -.
DR OrthoDB; 5297205at2; -.
DR PhylomeDB; O25743; -.
DR BRENDA; 3.4.19.13; 2604.
DR UniPathway; UPA00204; -.
DR EvolutionaryTrace; O25743; -.
DR PHI-base; PHI:3146; -.
DR Proteomes; UP000000429; Chromosome.
DR GO; GO:0036374; F:glutathione hydrolase activity; IEA:UniProtKB-UniRule.
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:UniProtKB-UniRule.
DR GO; GO:1902807; P:negative regulation of cell cycle G1/S phase transition; IDA:CACAO.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; IMP:CACAO.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IMP:CACAO.
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 NCBIfam; TIGR00066; g_glut_trans; 1.
DR PANTHER; PTHR43199; GLUTATHIONE HYDROLASE; 1.
DR PANTHER; PTHR43199:SF1; GLUTATHIONE HYDROLASE PROENZYME; 1.
DR Pfam; PF01019; G_glu_transpept; 1.
DR PRINTS; PR01210; GGTRANSPTASE.
DR SUPFAM; SSF56235; N-terminal nucleophile aminohydrolases (Ntn hydrolases); 1.
DR PROSITE; PS00462; G_GLU_TRANSPEPTIDASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure {ECO:0007829|PDB:2NQO, ECO:0007829|PDB:2QM6};
KW Acyltransferase {ECO:0000256|ARBA:ARBA00023315,
KW ECO:0000256|RuleBase:RU368036};
KW Glutathione biosynthesis {ECO:0000256|RuleBase:RU368036};
KW Hydrolase {ECO:0000256|ARBA:ARBA00022801, ECO:0000256|RuleBase:RU368036};
KW Reference proteome {ECO:0000313|Proteomes:UP000000429};
KW Transferase {ECO:0000256|ARBA:ARBA00022679, ECO:0000256|RuleBase:RU368036};
KW Zymogen {ECO:0000256|RuleBase:RU368036}.
FT ACT_SITE 380
FT /note="Nucleophile"
FT /evidence="ECO:0000256|PIRSR:PIRSR600101-1"
FT BINDING 103
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0007829|PDB:2QM6"
FT BINDING 400
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0007829|PDB:2QM6"
FT BINDING 419
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0007829|PDB:2QM6"
FT BINDING 422
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0007829|PDB:2QM6"
FT BINDING 451
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0007829|PDB:2QM6"
FT BINDING 452
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0007829|PDB:2QM6"
FT BINDING 472
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0007829|PDB:2QM6"
FT BINDING 473
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0007829|PDB:2QM6"
SQ SEQUENCE 567 AA; 61151 MW; 9A5B4E06B6B8967F CRC64;
MRRSFLKTIG LGVIALFLGL LNPLSAASYP PIKNTKVGLA LSSHPLASEI GQKVLEEGGN
AIDAAVAIGF ALAVVHPAAG NIGGGGFAVI HLANGENVAL DFREKAPLKA TKNMFLDKQG
NVVPKLSEDG YLAAGVPGTV AGMEAMLKKY GTKKLSQLID PAIKLAENGY AISQRQAETL
KEARERFLKY SSSKKYFFKK GHLDYQEGDL FVQKDLAKTL NQIKTLGAKG FYQGQVAELI
EKDMKKNGGI ITKEDLASYN VKWRKPVVGS YRGYKIISMS PPSSGGTHLI QILNVMENAD
LSALGYGASK NIHIAAEAMR QAYADRSVYM GDADFVSVPV DKLINKAYAK KIFDTIQPDT
VTPSSQIKPG MGQLHEGSNT THYSVADRWG NAVSVTYTIN ASYGSAASID GAGFLLNNEM
DDFSIKPGNP NLYGLVGGDA NAIEANKRPL SSMSPTIVLK NNKVFLVVGS PGGSRIITTV
LQVISNVIDY NMNISEAVSA PRFHMQWLPD ELRIEKFGMP ADVKDNLTKM GYQIVTKPVM
GDVNAIQVLP KTKGSVFYGS TDPRKEF
//
