ID   LGUL_YEAST              Reviewed;         326 AA.
AC   P50107; D6VZH1; Q9HFG0; Q9URB5;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   27-MAR-2024, entry version 186.
DE   RecName: Full=Glyoxalase I {ECO:0000303|PubMed:8824231};
DE            Short=Glx I {ECO:0000303|PubMed:8824231};
DE            EC=4.4.1.5 {ECO:0000269|PubMed:11050082, ECO:0000269|PubMed:8824231};
DE   AltName: Full=Aldoketomutase {ECO:0000305};
DE   AltName: Full=Ketone-aldehyde mutase {ECO:0000305};
DE   AltName: Full=Methylglyoxalase;
DE   AltName: Full=S-D-lactoylglutathione methylglyoxal lyase;
DE   AltName: Full=actoylglutathione lyase;
GN   Name=GLO1 {ECO:0000303|PubMed:8824231}; OrderedLocusNames=YML004C;
GN   ORFNames=YM9571.15C;
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], FUNCTION, CATALYTIC ACTIVITY,
RP   BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=8824231; DOI=10.1074/jbc.271.42.26194;
RA   Inoue Y., Kimura A.;
RT   "Identification of the structural gene for glyoxalase I from Saccharomyces
RT   cerevisiae.";
RL   J. Biol. Chem. 271:25958-25965(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY,
RP   BIOPHYSICOCHEMICAL PROPERTIES, ACTIVE SITE, SUBUNIT, AND PATHWAY.
RX   PubMed=11050082; DOI=10.1074/jbc.m005760200;
RA   Frickel E.M., Jemth P., Widersten M., Mannervik B.;
RT   "Yeast glyoxalase I is a monomeric enzyme with two active sites.";
RL   J. Biol. Chem. 276:1845-1849(2001).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9169872;
RA   Bowman S., Churcher C.M., Badcock K., Brown D., Chillingworth T.,
RA   Connor R., Dedman K., Devlin K., Gentles S., Hamlin N., Hunt S., Jagels K.,
RA   Lye G., Moule S., Odell C., Pearson D., Rajandream M.A., Rice P.,
RA   Skelton J., Walsh S.V., Whitehead S., Barrell B.G.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome XIII.";
RL   Nature 387:90-93(1997).
RN   [4]
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   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 310-326, AND PROTEIN SEQUENCE OF
RP   39-45; 150-165 AND 311-323.
RC   STRAIN=ATCC 26109 / X2180;
RX   PubMed=1777125;
RA   Inoue Y., Yano H., Ginya H., Tsuchiyama H., Murata K., Kimura A.;
RT   "Positive effect of GAC gene product on the mRNA level of glyoxalase I gene
RT   in Saccharomyces cerevisiae.";
RL   Biotechnol. Appl. Biochem. 14:391-394(1991).
RN   [6]
RP   DISCUSSION OF SEQUENCE.
RX   PubMed=8670139; DOI=10.1042/bj3161005;
RA   Ridderstroem M., Mannervik B.;
RT   "The primary structure of monomeric yeast glyoxalase I indicates a gene
RT   duplication resulting in two similar segments homologous with the subunit
RT   of dimeric human glyoxalase I.";
RL   Biochem. J. 316:1005-1006(1996).
RN   [7]
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).
CC   -!- FUNCTION: Catalyzes the conversion of hemimercaptal, formed from
CC       methylglyoxal and glutathione, to S-lactoylglutathione
CC       (PubMed:11050082, PubMed:8824231). Can use gamma-glutamylcysteine as a
CC       substrate (PubMed:8824231). {ECO:0000269|PubMed:11050082,
CC       ECO:0000269|PubMed:8824231}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(R)-S-lactoylglutathione = glutathione + methylglyoxal;
CC         Xref=Rhea:RHEA:19069, ChEBI:CHEBI:17158, ChEBI:CHEBI:57474,
CC         ChEBI:CHEBI:57925; EC=4.4.1.5; Evidence={ECO:0000269|PubMed:11050082,
CC         ECO:0000269|PubMed:8824231};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000250|UniProtKB:Q04760};
CC       Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q04760};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.41 mM for glutathione {ECO:0000269|PubMed:8824231};
CC         KM=1.2 mM for gamma-glutamylcysteine {ECO:0000269|PubMed:8824231};
CC   -!- PATHWAY: Secondary metabolite metabolism; methylglyoxal degradation;
CC       (R)-lactate from methylglyoxal: step 1/2. {ECO:0000269|PubMed:11050082,
CC       ECO:0000269|PubMed:8824231}.
CC   -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:11050082}.
CC   -!- MISCELLANEOUS: Present with 2570 molecules/cell in log phase SD medium.
CC       {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the glyoxalase I family. {ECO:0000305}.
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DR   EMBL; X99240; CAA67622.1; -; Genomic_DNA.
DR   EMBL; AJ297938; CAC16163.1; -; Genomic_DNA.
DR   EMBL; Z49810; CAA89948.1; -; Genomic_DNA.
DR   EMBL; S80483; AAB21302.1; -; Genomic_DNA.
DR   EMBL; BK006946; DAA09895.1; -; Genomic_DNA.
DR   PIR; S55115; S55115.
DR   RefSeq; NP_013710.1; NM_001182359.1.
DR   AlphaFoldDB; P50107; -.
DR   SMR; P50107; -.
DR   BioGRID; 35167; 52.
DR   STRING; 4932.YML004C; -.
DR   BindingDB; P50107; -.
DR   ChEMBL; CHEMBL6057; -.
DR   iPTMnet; P50107; -.
DR   MaxQB; P50107; -.
DR   PaxDb; 4932-YML004C; -.
DR   PeptideAtlas; P50107; -.
DR   EnsemblFungi; YML004C_mRNA; YML004C; YML004C.
DR   GeneID; 855009; -.
DR   KEGG; sce:YML004C; -.
DR   AGR; SGD:S000004463; -.
DR   SGD; S000004463; GLO1.
DR   VEuPathDB; FungiDB:YML004C; -.
DR   eggNOG; KOG2944; Eukaryota.
DR   GeneTree; ENSGT00390000012340; -.
DR   HOGENOM; CLU_046006_0_1_1; -.
DR   InParanoid; P50107; -.
DR   OMA; YWVEVIG; -.
DR   OrthoDB; 245930at2759; -.
DR   BioCyc; MetaCyc:YML004C-MONOMER; -.
DR   BioCyc; YEAST:YML004C-MONOMER; -.
DR   Reactome; R-SCE-70268; Pyruvate metabolism.
DR   SABIO-RK; P50107; -.
DR   UniPathway; UPA00619; UER00675.
DR   BioGRID-ORCS; 855009; 0 hits in 10 CRISPR screens.
DR   PRO; PR:P50107; -.
DR   Proteomes; UP000002311; Chromosome XIII.
DR   RNAct; P50107; Protein.
DR   GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR   GO; GO:0005634; C:nucleus; HDA:SGD.
DR   GO; GO:0004462; F:lactoylglutathione lyase activity; IMP:SGD.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0006749; P:glutathione metabolic process; IMP:SGD.
DR   GO; GO:0019243; P:methylglyoxal catabolic process to D-lactate via S-lactoyl-glutathione; IDA:SGD.
DR   CDD; cd07233; GlxI_Zn; 2.
DR   Gene3D; 3.10.180.10; 2,3-Dihydroxybiphenyl 1,2-Dioxygenase, domain 1; 2.
DR   InterPro; IPR029068; Glyas_Bleomycin-R_OHBP_Dase.
DR   InterPro; IPR004360; Glyas_Fos-R_dOase_dom.
DR   InterPro; IPR004361; Glyoxalase_1.
DR   InterPro; IPR018146; Glyoxalase_1_CS.
DR   InterPro; IPR037523; VOC.
DR   NCBIfam; TIGR00068; glyox_I; 2.
DR   PANTHER; PTHR10374:SF30; LACTOYLGLUTATHIONE LYASE; 1.
DR   PANTHER; PTHR10374; LACTOYLGLUTATHIONE LYASE GLYOXALASE I; 1.
DR   Pfam; PF00903; Glyoxalase; 2.
DR   SUPFAM; SSF54593; Glyoxalase/Bleomycin resistance protein/Dihydroxybiphenyl dioxygenase; 2.
DR   PROSITE; PS00934; GLYOXALASE_I_1; 2.
DR   PROSITE; PS00935; GLYOXALASE_I_2; 2.
DR   PROSITE; PS51819; VOC; 2.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Lyase; Metal-binding; Reference proteome;
KW   Repeat; Zinc.
FT   CHAIN           1..326
FT                   /note="Glyoxalase I"
FT                   /id="PRO_0000168087"
FT   DOMAIN          22..167
FT                   /note="VOC 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01163"
FT   DOMAIN          182..322
FT                   /note="VOC 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01163"
FT   ACT_SITE        163
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000269|PubMed:11050082"
FT   ACT_SITE        318
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000269|PubMed:11050082"
FT   BINDING         25
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /evidence="ECO:0000250"
FT   BINDING         29
FT                   /ligand="substrate"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /evidence="ECO:0000250|UniProtKB:Q04760"
FT   BINDING         89
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /evidence="ECO:0000250|UniProtKB:Q04760"
FT   BINDING         93
FT                   /ligand="substrate"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /evidence="ECO:0000250|UniProtKB:Q04760"
FT   BINDING         113
FT                   /ligand="substrate"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000250|UniProtKB:Q04760"
FT   BINDING         117
FT                   /ligand="substrate"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000250|UniProtKB:Q04760"
FT   BINDING         117
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000250|UniProtKB:Q04760"
FT   BINDING         147..148
FT                   /ligand="substrate"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000250|UniProtKB:Q04760"
FT   BINDING         163
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000250|UniProtKB:Q04760"
FT   CONFLICT        36
FT                   /note="T -> A (in Ref. 2; CAC16163)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        156
FT                   /note="G -> D (in Ref. 2; CAC16163 and 5; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        322
FT                   /note="H -> Y (in Ref. 2; CAC16163)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   326 AA;  37209 MW;  9726A8253F53FB2B CRC64;
     MSTDSTRYPI QIEKASNDPT LLLNHTCLRV KDPARTVKFY TEHFGMKLLS RKDFEEAKFS
     LYFLSFPKDD IPKNKNGEPD VFSAHGVLEL THNWGTEKNP DYKINNGNEE PHRGFGHICF
     SVSDINKTCE ELESQGVKFK KRLSEGRQKD IAFALGPDGY WIELITYSRE GQEYPKGSVG
     NKFNHTMIRI KNPTRSLEFY QNVLGMKLLR TSEHESAKFT LYFLGYGVPK TDSVFSCESV
     LELTHNWGTE NDPNFHYHNG NSEPQGYGHI CISCDDAGAL CKEIEVKYGD KIQWSPKFNQ
     GRMKNIAFLK DPDGYSIEVV PHGLIA
//