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 //