GSHR_PLAF7
ID GSHR_PLAF7 Reviewed; 546 AA.
AC O15770; A0A144A323; A0A144A3W0; Q8ILQ2;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 25-MAY-2022, sequence version 5.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Glutathione reductase {ECO:0000303|Ref.1};
DE Short=GRase {ECO:0000305};
DE Short=PfGR {ECO:0000303|PubMed:12729762};
DE EC=1.8.1.7 {ECO:0000269|PubMed:12729762};
DE Flags: Precursor;
GN Name=GR {ECO:0000303|PubMed:12729762}; Synonyms=GR3;
GN ORFNames=PF14_0192, PF3D7_1419800;
OS Plasmodium falciparum (isolate 3D7).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=36329;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Gilberger T.-W., Walter R.D., Mueller S.;
RT "Glutathione reductase from Plasmodium falciparum.";
RL Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7;
RX PubMed=12368864; DOI=10.1038/nature01097;
RA Gardner M.J., Hall N., Fung E., White O., Berriman M., Hyman R.W.,
RA Carlton J.M., Pain A., Nelson K.E., Bowman S., Paulsen I.T., James K.D.,
RA Eisen J.A., Rutherford K.M., Salzberg S.L., Craig A., Kyes S., Chan M.-S.,
RA Nene V., Shallom S.J., Suh B., Peterson J., Angiuoli S., Pertea M.,
RA Allen J., Selengut J., Haft D., Mather M.W., Vaidya A.B., Martin D.M.A.,
RA Fairlamb A.H., Fraunholz M.J., Roos D.S., Ralph S.A., McFadden G.I.,
RA Cummings L.M., Subramanian G.M., Mungall C., Venter J.C., Carucci D.J.,
RA Hoffman S.L., Newbold C., Davis R.W., Fraser C.M., Barrell B.G.;
RT "Genome sequence of the human malaria parasite Plasmodium falciparum.";
RL Nature 419:498-511(2002).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=12729762; DOI=10.1016/s0022-2836(03)00347-4;
RA Sarma G.N., Savvides S.N., Becker K., Schirmer M., Schirmer R.H.,
RA Karplus P.A.;
RT "Glutathione reductase of the malarial parasite Plasmodium falciparum:
RT crystal structure and inhibitor development.";
RL J. Mol. Biol. 328:893-907(2003).
RN [4]
RP SUBCELLULAR LOCATION, AND ALTERNATIVE INITIATION (ISOFORMS 1 AND 2).
RX PubMed=21203490; DOI=10.1371/journal.ppat.1001242;
RA Kehr S., Sturm N., Rahlfs S., Przyborski J.M., Becker K.;
RT "Compartmentation of redox metabolism in malaria parasites.";
RL PLoS Pathog. 6:e1001242-e1001242(2010).
CC -!- FUNCTION: Maintains high levels of reduced glutathione in the cytosol.
CC {ECO:0000269|PubMed:12729762}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 glutathione + NADP(+) = glutathione disulfide + H(+) +
CC NADPH; Xref=Rhea:RHEA:11740, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:57925, ChEBI:CHEBI:58297, ChEBI:CHEBI:58349; EC=1.8.1.7;
CC Evidence={ECO:0000269|PubMed:12729762};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:11742;
CC Evidence={ECO:0000269|PubMed:12729762};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:Q94655};
CC Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:Q94655};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=71 uM for glutathione disulfide (GSSG) (at 25 degrees Celsius and
CC pH 6.9) {ECO:0000269|PubMed:12729762};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q94655}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm
CC {ECO:0000269|PubMed:21203490}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Plastid, apicoplast
CC {ECO:0000269|PubMed:21203490}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=2;
CC IsoId=O15770-2; Sequence=Displayed;
CC Name=1;
CC IsoId=O15770-1; Sequence=VSP_061462;
CC -!- MISCELLANEOUS: [Isoform 1]: Produced by alternative initiation at Met-
CC 47 of isoform 2. {ECO:0000269|PubMed:21203490}.
CC -!- MISCELLANEOUS: The active site is a redox-active disulfide bond.
CC -!- SIMILARITY: Belongs to the class-I pyridine nucleotide-disulfide
CC oxidoreductase family. {ECO:0000305}.
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DR EMBL; AF027825; AAB84117.1; -; mRNA.
DR EMBL; LN999946; CZT99904.1; -; Genomic_DNA.
DR EMBL; LN999946; CZT99905.1; -; Genomic_DNA.
DR RefSeq; XP_001348365.1; XM_001348329.1.
DR AlphaFoldDB; O15770; -.
DR SMR; O15770; -.
DR STRING; 5833.PF14_0192; -.
DR BindingDB; O15770; -.
DR ChEMBL; CHEMBL5061; -.
DR DrugCentral; O15770; -.
DR PRIDE; O15770; -.
DR EnsemblProtists; CZT99904; CZT99904; PF3D7_1419800.1. [O15770-1]
DR EnsemblProtists; CZT99905; CZT99905; PF3D7_1419800.2. [O15770-2]
DR GeneID; 811773; -.
DR KEGG; pfa:PF3D7_1419800.1; -.
DR VEuPathDB; PlasmoDB:PF3D7_1419800; -.
DR HOGENOM; CLU_016755_2_2_1; -.
DR InParanoid; O15770; -.
DR OMA; MSKHYDY; -.
DR OrthoDB; 581771at2759; -.
DR PhylomeDB; O15770; -.
DR Reactome; R-PFA-3299685; Detoxification of Reactive Oxygen Species.
DR Reactome; R-PFA-499943; Interconversion of nucleotide di- and triphosphates.
DR Reactome; R-PFA-5263617; Metabolism of ingested MeSeO2H into MeSeH.
DR Reactome; R-PFA-5628897; TP53 Regulates Metabolic Genes.
DR Proteomes; UP000001450; Chromosome 14.
DR GO; GO:0020011; C:apicoplast; IDA:GeneDB.
DR GO; GO:0005737; C:cytoplasm; IDA:GeneDB.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0004362; F:glutathione-disulfide reductase (NADPH) activity; IDA:UniProtKB.
DR GO; GO:0004791; F:thioredoxin-disulfide reductase activity; IBA:GO_Central.
DR GO; GO:0045454; P:cell redox homeostasis; IBA:GO_Central.
DR GO; GO:0006979; P:response to oxidative stress; ISS:GeneDB.
DR Gene3D; 3.30.390.30; -; 1.
DR Gene3D; 3.50.50.60; -; 2.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR023753; FAD/NAD-binding_dom.
DR InterPro; IPR016156; FAD/NAD-linked_Rdtase_dimer_sf.
DR InterPro; IPR001100; Pyr_nuc-diS_OxRdtase.
DR InterPro; IPR004099; Pyr_nucl-diS_OxRdtase_dimer.
DR InterPro; IPR012999; Pyr_OxRdtase_I_AS.
DR Pfam; PF07992; Pyr_redox_2; 1.
DR Pfam; PF02852; Pyr_redox_dim; 1.
DR PIRSF; PIRSF000350; Mercury_reductase_MerA; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
DR SUPFAM; SSF55424; SSF55424; 1.
DR PROSITE; PS00076; PYRIDINE_REDOX_1; 1.
PE 1: Evidence at protein level;
KW Alternative initiation; Apicoplast; Cytoplasm; Disulfide bond; FAD;
KW Flavoprotein; NADP; Oxidoreductase; Plastid; Redox-active center;
KW Reference proteome; Transit peptide.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q94655"
FT TRANSIT 2..46
FT /note="Apicoplast"
FT /evidence="ECO:0000269|PubMed:21203490"
FT CHAIN 47..546
FT /note="Glutathione reductase"
FT /id="PRO_0000067960"
FT ACT_SITE 531
FT /note="Proton acceptor"
FT /evidence="ECO:0000305"
FT BINDING 58..59
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q94655"
FT BINDING 78..86
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q94655"
FT BINDING 94
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q94655"
FT BINDING 157
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q94655"
FT BINDING 358
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q94655"
FT BINDING 398..400
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q94655"
FT DISULFID 86..91
FT /note="Redox-active"
FT /evidence="ECO:0000250|UniProtKB:Q94655"
FT VAR_SEQ 1..46
FT /note="Missing (in isoform 1)"
FT /evidence="ECO:0000305"
FT /id="VSP_061462"
FT CONFLICT 329
FT /note="E -> G (in Ref. 1; AAB84117)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 546 AA; 62288 MW; 704318D61156ABB9 CRC64;
MYKHRYFHFF FFFFFFLVST KIIRSFTFLN NNTNLSNPVY FKKKANMVYD LIVIGGGSGG
MAAARRAARH NAKVALVEKS RLGGTCVNVG CVPKKIMFNA ASVHDILENS RHYGFDTKFS
FNLPLLVERR DKYIQRLNNI YRQNLSKDKV DLYEGTASFL SENRILIKGT KDNNNKDNGP
LNEEILEGRN ILIAVGNKPV FPPVKGIENT ISSDEFFNIK ESKKIGIVGS GYIAVELINV
IKRLGIDSYI FARGNRILRK FDESVINVLE NDMKKNNINI VTFADVVEIK KVSDKNLSIH
LSDGRIYEHF DHVIYCVGRS PDTENLNLEK LNVETNNNYI VVDENQRTSV NNIYAVGDCC
MVKKSKEIED LNLLKLYNEE TYLNKKENVT EDIFYNVQLT PVAINAGRLL ADRLFLKKTR
KTNYKLIPTV IFSHPPIGTI GLSEEAAIQI YGKENVKIYE SKFTNLFFSV YDIEPELKEK
TYLKLVCVGK DELIKGLHII GLNADEIVQG FAVALKMNAT KKDFDETIPI HPTAAEEFLT
LQPWMK
