ID   GSHB_YEAST              Reviewed;         491 AA.
AC   Q08220; D6W218;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   27-MAR-2024, entry version 192.
DE   RecName: Full=Glutathione synthetase GSH2 {ECO:0000303|PubMed:9512666};
DE            Short=GSH synthetase;
DE            Short=GSH-S;
DE            EC=6.3.2.3;
DE   AltName: Full=Glutathione synthase;
GN   Name=GSH2; OrderedLocusNames=YOL049W;
OS   Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX   NCBI_TaxID=559292;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND CATALYTIC ACTIVITY.
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9512666; DOI=10.1016/s0167-4781(97)00199-1;
RA   Inoue Y., Sugiyama K.I., Izawa S., Kimura A.;
RT   "Molecular identification of glutathione synthetase (GSH2) gene from
RT   Saccharomyces cerevisiae.";
RL   Biochim. Biophys. Acta 1395:315-320(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9169874;
RA   Dujon B., Albermann K., Aldea M., Alexandraki D., Ansorge W., Arino J.,
RA   Benes V., Bohn C., Bolotin-Fukuhara M., Bordonne R., Boyer J., Camasses A.,
RA   Casamayor A., Casas C., Cheret G., Cziepluch C., Daignan-Fornier B.,
RA   Dang V.-D., de Haan M., Delius H., Durand P., Fairhead C., Feldmann H.,
RA   Gaillon L., Galisson F., Gamo F.-J., Gancedo C., Goffeau A., Goulding S.E.,
RA   Grivell L.A., Habbig B., Hand N.J., Hani J., Hattenhorst U., Hebling U.,
RA   Hernando Y., Herrero E., Heumann K., Hiesel R., Hilger F., Hofmann B.,
RA   Hollenberg C.P., Hughes B., Jauniaux J.-C., Kalogeropoulos A.,
RA   Katsoulou C., Kordes E., Lafuente M.J., Landt O., Louis E.J., Maarse A.C.,
RA   Madania A., Mannhaupt G., Marck C., Martin R.P., Mewes H.-W., Michaux G.,
RA   Paces V., Parle-McDermott A.G., Pearson B.M., Perrin A., Pettersson B.,
RA   Poch O., Pohl T.M., Poirey R., Portetelle D., Pujol A., Purnelle B.,
RA   Ramezani Rad M., Rechmann S., Schwager C., Schweizer M., Sor F., Sterky F.,
RA   Tarassov I.A., Teodoru C., Tettelin H., Thierry A., Tobiasch E.,
RA   Tzermia M., Uhlen M., Unseld M., Valens M., Vandenbol M., Vetter I.,
RA   Vlcek C., Voet M., Volckaert G., Voss H., Wambutt R., Wedler H.,
RA   Wiemann S., Winsor B., Wolfe K.H., Zollner A., Zumstein E., Kleine K.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome XV.";
RL   Nature 387:98-102(1997).
RN   [3]
RP   GENOME REANNOTATION.
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=24374639; DOI=10.1534/g3.113.008995;
RA   Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA   Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA   Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT   "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL   G3 (Bethesda) 4:389-398(2014).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=17322287; DOI=10.1101/gr.6037607;
RA   Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA   Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA   Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA   Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA   LaBaer J.;
RT   "Approaching a complete repository of sequence-verified protein-encoding
RT   clones for Saccharomyces cerevisiae.";
RL   Genome Res. 17:536-543(2007).
RN   [5]
RP   LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX   PubMed=14562106; DOI=10.1038/nature02046;
RA   Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA   O'Shea E.K., Weissman J.S.;
RT   "Global analysis of protein expression in yeast.";
RL   Nature 425:737-741(2003).
RN   [6]
RP   X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH SUBSTRATE AND
RP   AMP-PNP, COFACTOR, AND SUBUNIT.
RX   PubMed=12467574; DOI=10.1016/s0969-2126(02)00906-1;
RA   Gogos A., Shapiro L.;
RT   "Large conformational changes in the catalytic cycle of glutathione
RT   synthase.";
RL   Structure 10:1669-1676(2002).
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + gamma-L-glutamyl-L-cysteine + glycine = ADP +
CC         glutathione + H(+) + phosphate; Xref=Rhea:RHEA:13557,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC         ChEBI:CHEBI:57305, ChEBI:CHEBI:57925, ChEBI:CHEBI:58173,
CC         ChEBI:CHEBI:456216; EC=6.3.2.3;
CC         Evidence={ECO:0000269|PubMed:9512666};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13558;
CC         Evidence={ECO:0000305|PubMed:9512666};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000269|PubMed:12467574};
CC       Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000269|PubMed:12467574};
CC   -!- PATHWAY: Sulfur metabolism; glutathione biosynthesis; glutathione from
CC       L-cysteine and L-glutamate: step 2/2.
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:12467574}.
CC   -!- MISCELLANEOUS: Present with 3430 molecules/cell in log phase SD medium.
CC       {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the eukaryotic GSH synthase family.
CC       {ECO:0000305}.
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DR   EMBL; Y13804; CAA74136.1; -; Genomic_DNA.
DR   EMBL; Z74791; CAA99054.1; -; Genomic_DNA.
DR   EMBL; AY723864; AAU09781.1; -; Genomic_DNA.
DR   EMBL; BK006948; DAA10734.1; -; Genomic_DNA.
DR   PIR; S66734; S66734.
DR   RefSeq; NP_014593.1; NM_001183303.1.
DR   PDB; 1M0T; X-ray; 2.30 A; A/B=1-491.
DR   PDB; 1M0W; X-ray; 1.80 A; A/B=1-491.
DR   PDBsum; 1M0T; -.
DR   PDBsum; 1M0W; -.
DR   AlphaFoldDB; Q08220; -.
DR   SMR; Q08220; -.
DR   BioGRID; 34354; 137.
DR   IntAct; Q08220; 1.
DR   STRING; 4932.YOL049W; -.
DR   iPTMnet; Q08220; -.
DR   MaxQB; Q08220; -.
DR   PaxDb; 4932-YOL049W; -.
DR   PeptideAtlas; Q08220; -.
DR   EnsemblFungi; YOL049W_mRNA; YOL049W; YOL049W.
DR   GeneID; 854108; -.
DR   KEGG; sce:YOL049W; -.
DR   AGR; SGD:S000005409; -.
DR   SGD; S000005409; GSH2.
DR   VEuPathDB; FungiDB:YOL049W; -.
DR   eggNOG; KOG0021; Eukaryota.
DR   GeneTree; ENSGT00390000013764; -.
DR   HOGENOM; CLU_025152_2_1_1; -.
DR   InParanoid; Q08220; -.
DR   OMA; NGLVMYP; -.
DR   OrthoDB; 1448at2759; -.
DR   BioCyc; YEAST:YOL049W-MONOMER; -.
DR   BRENDA; 6.3.2.3; 984.
DR   Reactome; R-SCE-174403; Glutathione synthesis and recycling.
DR   UniPathway; UPA00142; UER00210.
DR   BioGRID-ORCS; 854108; 0 hits in 10 CRISPR screens.
DR   EvolutionaryTrace; Q08220; -.
DR   PRO; PR:Q08220; -.
DR   Proteomes; UP000002311; Chromosome XV.
DR   RNAct; Q08220; Protein.
DR   GO; GO:0005737; C:cytoplasm; TAS:SGD.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR   GO; GO:0043295; F:glutathione binding; IDA:UniProtKB.
DR   GO; GO:0004363; F:glutathione synthase activity; IDA:SGD.
DR   GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR   GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR   GO; GO:0006750; P:glutathione biosynthetic process; IMP:SGD.
DR   Gene3D; 3.30.1490.50; -; 1.
DR   Gene3D; 3.30.1490.80; -; 1.
DR   Gene3D; 3.30.470.20; ATP-grasp fold, B domain; 1.
DR   Gene3D; 3.40.50.1760; Glutathione synthase, substrate-binding domain superfamily, eukaryotic; 1.
DR   InterPro; IPR005615; Glutathione_synthase.
DR   InterPro; IPR014042; Glutathione_synthase_a-hlx.
DR   InterPro; IPR014709; Glutathione_synthase_C_euk.
DR   InterPro; IPR014049; Glutathione_synthase_N_euk.
DR   InterPro; IPR037013; GSH-S_sub-bd_sf.
DR   InterPro; IPR004887; GSH_synth_subst-bd.
DR   InterPro; IPR016185; PreATP-grasp_dom_sf.
DR   NCBIfam; TIGR01986; glut_syn_euk; 1.
DR   PANTHER; PTHR11130; GLUTATHIONE SYNTHETASE; 1.
DR   PANTHER; PTHR11130:SF0; GLUTATHIONE SYNTHETASE; 1.
DR   Pfam; PF03917; GSH_synth_ATP; 1.
DR   Pfam; PF03199; GSH_synthase; 1.
DR   PIRSF; PIRSF001558; GSHase; 1.
DR   SUPFAM; SSF56059; Glutathione synthetase ATP-binding domain-like; 1.
DR   SUPFAM; SSF52440; PreATP-grasp domain; 1.
PE   1: Evidence at protein level;
KW   3D-structure; ATP-binding; Glutathione biosynthesis; Ligase; Magnesium;
KW   Metal-binding; Nucleotide-binding; Reference proteome.
FT   CHAIN           1..491
FT                   /note="Glutathione synthetase GSH2"
FT                   /id="PRO_0000211266"
FT   BINDING         128
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000269|PubMed:12467574"
FT   BINDING         146
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT   BINDING         146
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT   BINDING         148
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250"
FT   BINDING         150..153
FT                   /ligand="substrate"
FT   BINDING         228..230
FT                   /ligand="substrate"
FT   BINDING         234
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000269|PubMed:12467574"
FT   BINDING         285..288
FT                   /ligand="substrate"
FT   BINDING         324
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT   BINDING         382..391
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT   BINDING         386
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT   BINDING         393
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT   BINDING         415..418
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT   BINDING         442
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT   BINDING         467
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         469
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT   BINDING         475
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250"
FT   BINDING         478..479
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   HELIX           8..25
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   HELIX           34..36
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   STRAND          40..43
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   STRAND          46..49
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   STRAND          51..54
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   HELIX           55..79
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   HELIX           85..96
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   TURN            97..100
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   HELIX           101..111
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   STRAND          123..136
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   STRAND          139..148
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   HELIX           155..170
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   HELIX           183..185
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   HELIX           191..208
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   STRAND          219..224
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   HELIX           231..243
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   STRAND          249..252
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   HELIX           254..260
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   STRAND          261..263
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   TURN            265..267
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   STRAND          270..272
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   TURN            273..275
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   STRAND          278..286
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   HELIX           290..292
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   HELIX           296..307
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   STRAND          308..313
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   HELIX           316..321
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   HELIX           324..329
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   HELIX           333..336
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   TURN            337..339
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   HELIX           343..350
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   STRAND          356..358
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   STRAND          360..362
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   HELIX           363..374
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   HELIX           376..378
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   STRAND          379..385
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   HELIX           394..396
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   HELIX           397..402
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   HELIX           406..411
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   STRAND          412..416
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   STRAND          428..430
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   STRAND          433..435
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   STRAND          439..451
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   STRAND          456..469
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   STRAND          472..474
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   STRAND          477..480
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   STRAND          483..485
FT                   /evidence="ECO:0007829|PDB:1M0W"
FT   STRAND          488..491
FT                   /evidence="ECO:0007829|PDB:1M0W"
SQ   SEQUENCE   491 AA;  55815 MW;  D2AE50A487E0791C CRC64;
     MAHYPPSKDQ LNELIQEVNQ WAITNGLSMY PPKFEENPSN ASVSPVTIYP TPIPRKCFDE
     AVQIQPVFNE LYARITQDMA QPDSYLHKTT EALALSDSEF TGKLWSLYLA TLKSAQYKKQ
     NFRLGIFRSD YLIDKKKGTE QIKQVEFNTV SVSFAGLSEK VDRLHSYLNR ANKYDPKGPI
     YNDQNMVISD SGYLLSKALA KAVESYKSQQ SSSTTSDPIV AFIVQRNERN VFDQKVLELN
     LLEKFGTKSV RLTFDDVNDK LFIDDKTGKL FIRDTEQEIA VVYYRTGYTT TDYTSEKDWE
     ARLFLEKSFA IKAPDLLTQL SGSKKIQQLL TDEGVLGKYI SDAEKKSSLL KTFVKIYPLD
     DTKLGREGKR LALSEPSKYV LKPQREGGGN NVYKENIPNF LKGIEERHWD AYILMELIEP
     ELNENNIILR DNKSYNEPII SELGIYGCVL FNDEQVLSNE FSGSLLRSKF NTSNEGGVAA
     GFGCLDSIIL Y
//