ID GSHR_PLAFK Reviewed; 500 AA.
AC Q94655;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 08-NOV-2023, entry version 127.
DE RecName: Full=Glutathione reductase {ECO:0000303|PubMed:8774709};
DE Short=GRase {ECO:0000305};
DE Short=PfGR {ECO:0000303|PubMed:12729762};
DE EC=1.8.1.7 {ECO:0000269|PubMed:12729762, ECO:0000269|PubMed:8631352};
GN Name=GR {ECO:0000303|PubMed:8631352};
GN Synonyms=GR2 {ECO:0000303|PubMed:8774709};
OS Plasmodium falciparum (isolate K1 / Thailand).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=5839;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND DEVELOPMENTAL STAGE.
RX PubMed=8774709; DOI=10.1111/j.1432-1033.1996.0655u.x;
RA Faerber P.M., Becker K., Mueller S.;
RT "Molecular cloning and characterization of a putative glutathione reductase
RT gene, the PfGR2 gene, from Plasmodium falciparum.";
RL Eur. J. Biochem. 239:655-661(1996).
RN [2]
RP PROTEIN SEQUENCE OF 2-16, FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND DEVELOPMENTAL STAGE.
RX PubMed=8631352; DOI=10.1111/j.1432-1033.1996.00345.x;
RA Krauth-Siegel R.L., Muller J.G., Lottspeich F., Schirmer R.H.;
RT "Glutathione reductase and glutamate dehydrogenase of Plasmodium
RT falciparum, the causative agent of tropical malaria.";
RL Eur. J. Biochem. 235:345-350(1996).
RN [3] {ECO:0007744|PDB:1ONF}
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) IN COMPLEX WITH FAD, FUNCTION,
RP CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, AND DISULFIDE
RP BOND.
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).
CC -!- FUNCTION: Maintains high levels of reduced glutathione in the cytosol.
CC {ECO:0000269|PubMed:12729762, ECO:0000269|PubMed:8631352}.
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, ECO:0000269|PubMed:8631352};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:11742;
CC Evidence={ECO:0000269|PubMed:12729762, ECO:0000269|PubMed:8631352};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:8631352};
CC Note=Binds 1 FAD per subunit. {ECO:0000269|PubMed:12729762};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.8 uM for NADPH (at 25 degrees Celsius and pH 6.9)
CC {ECO:0000269|PubMed:8631352};
CC KM=69 uM for glutathione disulfide (GSSG) (at 25 degrees Celsius and
CC pH 6.9) {ECO:0000269|PubMed:8631352};
CC KM=88 uM for glutathione disulfide (GSSG) (at 25 degrees Celsius and
CC pH 6.9) {ECO:0000269|PubMed:12729762};
CC Note=kcat is 188.3 sec(-1) with GSSG as substrate (at 25 degrees
CC Celsius and pH 6.9). {ECO:0000269|PubMed:8631352};
CC pH dependence:
CC Optimum pH is 6.8. {ECO:0000269|PubMed:8631352};
CC Temperature dependence:
CC Inactive at 80 degrees Celsius. {ECO:0000269|PubMed:8631352};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:8631352}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O15770}.
CC -!- DEVELOPMENTAL STAGE: Expressed during the parasite blood stage,
CC including in schizonts (at protein level) (PubMed:8631352). Expression
CC is weak in ring, early trophozoite and increases in the late
CC trophozoite and early schizont stage (PubMed:8774709).
CC {ECO:0000269|PubMed:8631352, ECO:0000269|PubMed:8774709}.
CC -!- MISCELLANEOUS: There are 2 isoforms resulting from alternative
CC translation initiation. The displayed sequence is likely to represent
CC the shorter isoform. {ECO:0000305}.
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}.
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; X93462; CAA63747.1; -; Genomic_DNA.
DR PDB; 1ONF; X-ray; 2.60 A; A=1-500.
DR PDBsum; 1ONF; -.
DR AlphaFoldDB; Q94655; -.
DR SMR; Q94655; -.
DR ChEMBL; CHEMBL1741261; -.
DR DrugBank; DB03147; Flavin adenine dinucleotide.
DR EvolutionaryTrace; Q94655; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0004362; F:glutathione-disulfide reductase (NADP) activity; IEA:UniProtKB-EC.
DR GO; GO:0045454; P:cell redox homeostasis; IEA:InterPro.
DR Gene3D; 3.30.390.30; -; 1.
DR Gene3D; 3.50.50.60; FAD/NAD(P)-binding domain; 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; IPR046952; GSHR/TRXR-like.
DR InterPro; IPR001100; Pyr_nuc-diS_OxRdtase.
DR InterPro; IPR004099; Pyr_nucl-diS_OxRdtase_dimer.
DR InterPro; IPR012999; Pyr_OxRdtase_I_AS.
DR PANTHER; PTHR42737; GLUTATHIONE REDUCTASE; 1.
DR PANTHER; PTHR42737:SF2; GLUTATHIONE REDUCTASE; 1.
DR Pfam; PF07992; Pyr_redox_2; 1.
DR Pfam; PF02852; Pyr_redox_dim; 1.
DR PIRSF; PIRSF000350; Mercury_reductase_MerA; 1.
DR PRINTS; PR00368; FADPNR.
DR PRINTS; PR00411; PNDRDTASEI.
DR SUPFAM; SSF51905; FAD/NAD(P)-binding domain; 1.
DR SUPFAM; SSF55424; FAD/NAD-linked reductases, dimerisation (C-terminal) domain; 1.
DR PROSITE; PS00076; PYRIDINE_REDOX_1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Direct protein sequencing; Disulfide bond; FAD;
KW Flavoprotein; NADP; Oxidoreductase; Redox-active center.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:8631352"
FT CHAIN 2..500
FT /note="Glutathione reductase"
FT /id="PRO_0000067959"
FT ACT_SITE 485
FT /note="Proton acceptor"
FT /evidence="ECO:0000305"
FT BINDING 12..13
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:12729762,
FT ECO:0007744|PDB:1ONF"
FT BINDING 32..40
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:12729762,
FT ECO:0007744|PDB:1ONF"
FT BINDING 48
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:12729762,
FT ECO:0007744|PDB:1ONF"
FT BINDING 111
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:12729762,
FT ECO:0007744|PDB:1ONF"
FT BINDING 312
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:12729762,
FT ECO:0007744|PDB:1ONF"
FT BINDING 352..354
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:12729762,
FT ECO:0007744|PDB:1ONF"
FT DISULFID 40..45
FT /note="Redox-active"
FT /evidence="ECO:0000269|PubMed:12729762,
FT ECO:0007744|PDB:1ONF"
FT STRAND 3..8
FT /evidence="ECO:0007829|PDB:1ONF"
FT HELIX 12..23
FT /evidence="ECO:0007829|PDB:1ONF"
FT STRAND 28..35
FT /evidence="ECO:0007829|PDB:1ONF"
FT HELIX 38..42
FT /evidence="ECO:0007829|PDB:1ONF"
FT HELIX 45..63
FT /evidence="ECO:0007829|PDB:1ONF"
FT HELIX 64..67
FT /evidence="ECO:0007829|PDB:1ONF"
FT HELIX 77..101
FT /evidence="ECO:0007829|PDB:1ONF"
FT STRAND 105..109
FT /evidence="ECO:0007829|PDB:1ONF"
FT STRAND 142..147
FT /evidence="ECO:0007829|PDB:1ONF"
FT HELIX 161..163
FT /evidence="ECO:0007829|PDB:1ONF"
FT HELIX 167..170
FT /evidence="ECO:0007829|PDB:1ONF"
FT STRAND 177..182
FT /evidence="ECO:0007829|PDB:1ONF"
FT HELIX 186..196
FT /evidence="ECO:0007829|PDB:1ONF"
FT TURN 197..199
FT /evidence="ECO:0007829|PDB:1ONF"
FT STRAND 201..205
FT /evidence="ECO:0007829|PDB:1ONF"
FT STRAND 207..211
FT /evidence="ECO:0007829|PDB:1ONF"
FT HELIX 217..229
FT /evidence="ECO:0007829|PDB:1ONF"
FT STRAND 233..235
FT /evidence="ECO:0007829|PDB:1ONF"
FT STRAND 240..247
FT /evidence="ECO:0007829|PDB:1ONF"
FT STRAND 251..255
FT /evidence="ECO:0007829|PDB:1ONF"
FT STRAND 260..269
FT /evidence="ECO:0007829|PDB:1ONF"
FT TURN 276..279
FT /evidence="ECO:0007829|PDB:1ONF"
FT TURN 283..286
FT /evidence="ECO:0007829|PDB:1ONF"
FT STRAND 289..292
FT /evidence="ECO:0007829|PDB:1ONF"
FT STRAND 294..296
FT /evidence="ECO:0007829|PDB:1ONF"
FT STRAND 303..309
FT /evidence="ECO:0007829|PDB:1ONF"
FT STRAND 314..316
FT /evidence="ECO:0007829|PDB:1ONF"
FT HELIX 354..369
FT /evidence="ECO:0007829|PDB:1ONF"
FT STRAND 383..385
FT /evidence="ECO:0007829|PDB:1ONF"
FT STRAND 391..395
FT /evidence="ECO:0007829|PDB:1ONF"
FT HELIX 398..404
FT /evidence="ECO:0007829|PDB:1ONF"
FT HELIX 407..409
FT /evidence="ECO:0007829|PDB:1ONF"
FT STRAND 410..417
FT /evidence="ECO:0007829|PDB:1ONF"
FT HELIX 420..422
FT /evidence="ECO:0007829|PDB:1ONF"
FT HELIX 429..431
FT /evidence="ECO:0007829|PDB:1ONF"
FT STRAND 435..442
FT /evidence="ECO:0007829|PDB:1ONF"
FT TURN 443..446
FT /evidence="ECO:0007829|PDB:1ONF"
FT STRAND 447..455
FT /evidence="ECO:0007829|PDB:1ONF"
FT HELIX 458..470
FT /evidence="ECO:0007829|PDB:1ONF"
FT HELIX 475..479
FT /evidence="ECO:0007829|PDB:1ONF"
FT HELIX 491..494
FT /evidence="ECO:0007829|PDB:1ONF"
SQ SEQUENCE 500 AA; 56561 MW; AB2299144002FCD3 CRC64;
MVYDLIVIGG GSGGMAAARR AARHNAKVAL VEKSRLGGTC VNVGCVPKKI MFNAASVHDI
LENSRHYGFD TKFSFNLPLL VERRDKYIQR LNNIYRQNLS KDKVDLYEGT ASFLSENRIL
IKGTKDNNNK DNGPLNEEIL EGRNILIAVG NKPVFPPVKG IENTISSDEF FNIKESKKIG
IVGSGYIAVE LINVIKRLGI DSYIFARGNR ILRKFDESVI NVLENDMKKN NINIVTFADV
VEIKKVSDKN LSIHLSDGRI YEHFDHVIYC VGRSPDTENL KLEKLNVETN NNYIVVDENQ
RTSVNNIYAV GDCCMVKKSK EIEDLNLLKL YNEERYLNKK ENVTEDIFYN VQLTPVAINA
GRLLADRLFL KKTRKTNYKL IPTVIFSHPP IGTIGLSEEA AIQIYGKENV KIYESKFTNL
FFSVYDIEPE LKEKTYLKLV CVGKDELIKG LHIIGLNADE IVQGFAVALK MNATKKDFDE
TIPIHPTAAE EFLTLQPWMK
//
