ID   GST_PLAF7               Reviewed;         211 AA.
AC   Q8ILQ7; A0A144A1J6; Q8MU52; Q95V54;
DT   28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 1.
DT   27-MAR-2024, entry version 120.
DE   RecName: Full=Glutathione S-transferase {ECO:0000303|PubMed:12108547};
DE            Short=PfGST {ECO:0000303|PubMed:12108547};
DE            EC=2.5.1.18 {ECO:0000269|PubMed:12108547, ECO:0000269|PubMed:12387854, ECO:0000269|PubMed:14623980, ECO:0000269|PubMed:15888443};
GN   Name=GST {ECO:0000303|PubMed:12108547};
GN   ORFNames=PF14_0187, PF3D7_1419300;
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], FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP   REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RX   PubMed=12108547; DOI=10.1515/bc.2002.086;
RA   Harwaldt P., Rahlfs S., Becker K.;
RT   "Glutathione S-transferase of the malarial parasite Plasmodium falciparum:
RT   characterization of a potential drug target.";
RL   Biol. Chem. 383:821-830(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP   REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RX   PubMed=12387854; DOI=10.1016/s0166-6851(02)00160-3;
RA   Liebau E., Bergmann B., Campbell A.M., Teesdale-Spittle P., Brophy P.M.,
RA   Lueersen K., Walter R.D.;
RT   "The glutathione S-transferase from Plasmodium falciparum.";
RL   Mol. Biochem. Parasitol. 124:85-90(2002).
RN   [3]
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   [4]
RP   CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=15888443; DOI=10.1074/jbc.m503889200;
RA   Liebau E., De Maria F., Burmeister C., Perbandt M., Turella P.,
RA   Antonini G., Federici G., Giansanti F., Stella L., Lo Bello M.,
RA   Caccuri A.M., Ricci G.;
RT   "Cooperativity and pseudo-cooperativity in the glutathione S-transferase
RT   from Plasmodium falciparum.";
RL   J. Biol. Chem. 280:26121-26128(2005).
RN   [5]
RP   X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS), AND CATALYTIC ACTIVITY.
RX   PubMed=14623980; DOI=10.1073/pnas.2333763100;
RA   Fritz-Wolf K., Becker A., Rahlfs S., Harwaldt P., Schirmer R.H., Kabsch W.,
RA   Becker K.;
RT   "X-ray structure of glutathione S-transferase from the malarial parasite
RT   Plasmodium falciparum.";
RL   Proc. Natl. Acad. Sci. U.S.A. 100:13821-13826(2003).
RN   [6]
RP   X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH S-HEXYL GLUTATHIONE.
RX   PubMed=12972411; DOI=10.1074/jbc.m309663200;
RA   Perbandt M., Burmeister C., Walter R.D., Betzel C., Liebau E.;
RT   "Native and inhibited structure of a Mu class-related glutathione S-
RT   transferase from Plasmodium falciparum.";
RL   J. Biol. Chem. 279:1336-1342(2004).
RN   [7]
RP   X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH S-HEXYL GLUTATHIONE,
RP   FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND MUTAGENESIS OF TYR-9;
RP   LYS-15; GLN-71; CYS-101 AND TYR-211.
RX   PubMed=16385005; DOI=10.1110/ps.051891106;
RA   Hiller N., Fritz-Wolf K., Deponte M., Wende W., Zimmermann H., Becker K.;
RT   "Plasmodium falciparum glutathione S-transferase -- structural and
RT   mechanistic studies on ligand binding and enzyme inhibition.";
RL   Protein Sci. 15:281-289(2006).
CC   -!- FUNCTION: Conjugation of reduced glutathione to a wide number of
CC       exogenous and endogenous hydrophobic electrophiles. May also function
CC       as a storage protein or ligandin for parasitotoxic ferriprotoporphyrin
CC       IX (hemin). {ECO:0000269|PubMed:12108547, ECO:0000269|PubMed:12387854,
CC       ECO:0000269|PubMed:16385005}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=glutathione + RX = a halide anion + an S-substituted
CC         glutathione + H(+); Xref=Rhea:RHEA:16437, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:16042, ChEBI:CHEBI:17792, ChEBI:CHEBI:57925,
CC         ChEBI:CHEBI:90779; EC=2.5.1.18;
CC         Evidence={ECO:0000269|PubMed:12108547, ECO:0000269|PubMed:12387854,
CC         ECO:0000269|PubMed:14623980, ECO:0000269|PubMed:15888443};
CC   -!- ACTIVITY REGULATION: Inhibited by chloroquine, cibacron blue,
CC       ferriprotoporphyrin IX (hemin) and S-hexylglutathione.
CC       {ECO:0000269|PubMed:12108547, ECO:0000269|PubMed:12387854,
CC       ECO:0000269|PubMed:15888443}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.156 mM for bromosulphophthalein {ECO:0000269|PubMed:12108547,
CC         ECO:0000269|PubMed:12387854, ECO:0000269|PubMed:15888443,
CC         ECO:0000269|PubMed:16385005};
CC         KM=10 mM for 1-chloro-2,4-dinitrobenzene
CC         {ECO:0000269|PubMed:12108547, ECO:0000269|PubMed:12387854,
CC         ECO:0000269|PubMed:15888443, ECO:0000269|PubMed:16385005};
CC         KM=2.5 mM for 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole
CC         {ECO:0000269|PubMed:12108547, ECO:0000269|PubMed:12387854,
CC         ECO:0000269|PubMed:15888443, ECO:0000269|PubMed:16385005};
CC         KM=0.96 mM for ethacrynic acid {ECO:0000269|PubMed:12108547,
CC         ECO:0000269|PubMed:12387854, ECO:0000269|PubMed:15888443,
CC         ECO:0000269|PubMed:16385005};
CC         KM=0.164 mM for reduced glutathione {ECO:0000269|PubMed:12108547,
CC         ECO:0000269|PubMed:12387854, ECO:0000269|PubMed:15888443,
CC         ECO:0000269|PubMed:16385005};
CC       pH dependence:
CC         Optimum pH is 8.1. {ECO:0000269|PubMed:12108547,
CC         ECO:0000269|PubMed:12387854, ECO:0000269|PubMed:15888443,
CC         ECO:0000269|PubMed:16385005};
CC   -!- SUBUNIT: Homodimer. In the absence of ligands two homodimers may
CC       interact to form a tetramer. {ECO:0000269|PubMed:12108547,
CC       ECO:0000269|PubMed:12387854, ECO:0000269|PubMed:16385005}.
CC   -!- SIMILARITY: Belongs to the GST superfamily. {ECO:0000305}.
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DR   EMBL; AY014840; AAK00582.1; -; mRNA.
DR   EMBL; AF426836; AAL25087.1; -; mRNA.
DR   EMBL; LN999946; CZT99899.1; -; Genomic_DNA.
DR   RefSeq; XP_001348360.1; XM_001348324.1.
DR   PDB; 1OKT; X-ray; 1.90 A; A/B=1-211.
DR   PDB; 1PA3; X-ray; 2.70 A; A/B=1-211.
DR   PDB; 1Q4J; X-ray; 2.20 A; A/B=1-211.
DR   PDB; 2AAW; X-ray; 2.40 A; A/C=1-211.
DR   PDB; 3FR3; X-ray; 1.90 A; A/B=1-211.
DR   PDB; 3FR6; X-ray; 2.60 A; A/B=1-211.
DR   PDB; 3FR9; X-ray; 2.40 A; A/B=1-211.
DR   PDB; 3FRC; X-ray; 2.00 A; A/B=1-211.
DR   PDB; 4ZXG; X-ray; 1.70 A; A/B=3-207.
DR   PDBsum; 1OKT; -.
DR   PDBsum; 1PA3; -.
DR   PDBsum; 1Q4J; -.
DR   PDBsum; 2AAW; -.
DR   PDBsum; 3FR3; -.
DR   PDBsum; 3FR6; -.
DR   PDBsum; 3FR9; -.
DR   PDBsum; 3FRC; -.
DR   PDBsum; 4ZXG; -.
DR   AlphaFoldDB; Q8ILQ7; -.
DR   SMR; Q8ILQ7; -.
DR   STRING; 36329.Q8ILQ7; -.
DR   BindingDB; Q8ILQ7; -.
DR   ChEMBL; CHEMBL1697656; -.
DR   DrugBank; DB00608; Chloroquine.
DR   DrugBank; DB01942; Formic acid.
DR   DrugBank; DB04132; S-Hexylglutathione.
DR   PaxDb; 5833-PF14_0187; -.
DR   EnsemblProtists; CZT99899; CZT99899; PF3D7_1419300.
DR   GeneID; 811768; -.
DR   KEGG; pfa:PF3D7_1419300; -.
DR   VEuPathDB; PlasmoDB:PF3D7_1419300; -.
DR   VEuPathDB; PlasmoDB:Pf7G8-2_000494300; -.
DR   VEuPathDB; PlasmoDB:Pf7G8_140024800; -.
DR   VEuPathDB; PlasmoDB:PfCD01_140025000; -.
DR   VEuPathDB; PlasmoDB:PfDd2_140024100; -.
DR   VEuPathDB; PlasmoDB:PfGA01_140025100; -.
DR   VEuPathDB; PlasmoDB:PfGB4_140025700; -.
DR   VEuPathDB; PlasmoDB:PfGN01_140024800; -.
DR   VEuPathDB; PlasmoDB:PfHB3_140025300; -.
DR   VEuPathDB; PlasmoDB:PfIT_140026000; -.
DR   VEuPathDB; PlasmoDB:PfKE01_140024600; -.
DR   VEuPathDB; PlasmoDB:PfKH01_140025000; -.
DR   VEuPathDB; PlasmoDB:PfKH02_140025300; -.
DR   VEuPathDB; PlasmoDB:PfML01_140024800; -.
DR   VEuPathDB; PlasmoDB:PfNF135_140024700; -.
DR   VEuPathDB; PlasmoDB:PfNF166_140023400; -.
DR   VEuPathDB; PlasmoDB:PfNF54_140024300; -.
DR   VEuPathDB; PlasmoDB:PfSD01_140022900; -.
DR   VEuPathDB; PlasmoDB:PfSN01_140026700; -.
DR   VEuPathDB; PlasmoDB:PfTG01_140024900; -.
DR   HOGENOM; CLU_039475_1_0_1; -.
DR   OMA; INMYAEG; -.
DR   OrthoDB; 1385810at2759; -.
DR   PhylomeDB; Q8ILQ7; -.
DR   BRENDA; 2.5.1.18; 4889.
DR   Reactome; R-PFA-156590; Glutathione conjugation.
DR   Reactome; R-PFA-2162123; Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
DR   Proteomes; UP000001450; Chromosome 14.
DR   GO; GO:0004364; F:glutathione transferase activity; IDA:GeneDB.
DR   CDD; cd03192; GST_C_Sigma_like; 1.
DR   CDD; cd03039; GST_N_Sigma_like; 1.
DR   Gene3D; 1.20.1050.10; -; 1.
DR   Gene3D; 3.40.30.10; Glutaredoxin; 1.
DR   InterPro; IPR010987; Glutathione-S-Trfase_C-like.
DR   InterPro; IPR036282; Glutathione-S-Trfase_C_sf.
DR   InterPro; IPR040079; Glutathione_S-Trfase.
DR   InterPro; IPR004045; Glutathione_S-Trfase_N.
DR   InterPro; IPR004046; GST_C.
DR   InterPro; IPR036249; Thioredoxin-like_sf.
DR   PANTHER; PTHR11571; GLUTATHIONE S-TRANSFERASE; 1.
DR   PANTHER; PTHR11571:SF224; HEMATOPOIETIC PROSTAGLANDIN D SYNTHASE; 1.
DR   Pfam; PF14497; GST_C_3; 1.
DR   Pfam; PF02798; GST_N; 1.
DR   SFLD; SFLDG01205; AMPS.1; 1.
DR   SFLD; SFLDS00019; Glutathione_Transferase_(cytos; 1.
DR   SUPFAM; SSF47616; GST C-terminal domain-like; 1.
DR   SUPFAM; SSF52833; Thioredoxin-like; 1.
DR   PROSITE; PS50405; GST_CTER; 1.
DR   PROSITE; PS50404; GST_NTER; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Reference proteome; Transferase.
FT   CHAIN           1..211
FT                   /note="Glutathione S-transferase"
FT                   /id="PRO_0000259967"
FT   DOMAIN          3..87
FT                   /note="GST N-terminal"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          89..211
FT                   /note="GST C-terminal"
FT                   /evidence="ECO:0000255"
FT   BINDING         58..59
FT                   /ligand="glutathione"
FT                   /ligand_id="ChEBI:CHEBI:57925"
FT                   /evidence="ECO:0000305|PubMed:12972411"
FT   BINDING         71..72
FT                   /ligand="glutathione"
FT                   /ligand_id="ChEBI:CHEBI:57925"
FT                   /evidence="ECO:0000305|PubMed:12972411"
FT   BINDING         105
FT                   /ligand="glutathione"
FT                   /ligand_id="ChEBI:CHEBI:57925"
FT                   /evidence="ECO:0007744|PDB:3FR9"
FT   BINDING         117
FT                   /ligand="glutathione"
FT                   /ligand_id="ChEBI:CHEBI:57925"
FT                   /evidence="ECO:0000305|PubMed:12972411"
FT   BINDING         121
FT                   /ligand="glutathione"
FT                   /ligand_id="ChEBI:CHEBI:57925"
FT                   /evidence="ECO:0000305|PubMed:12972411"
FT   MUTAGEN         9
FT                   /note="Y->F: Greater than 10-fold decrease in activity."
FT                   /evidence="ECO:0000269|PubMed:16385005"
FT   MUTAGEN         15
FT                   /note="K->E: 10-fold decrease in substrate affinity and
FT                   20-fold decrease in activity."
FT                   /evidence="ECO:0000269|PubMed:16385005"
FT   MUTAGEN         71
FT                   /note="Q->E: 3-fold decrease in substrate affinity and
FT                   2-fold decrease in activity."
FT                   /evidence="ECO:0000269|PubMed:16385005"
FT   MUTAGEN         101
FT                   /note="C->A: 2-fold decrease in substrate affinity."
FT                   /evidence="ECO:0000269|PubMed:16385005"
FT   MUTAGEN         211
FT                   /note="Y->F: 2-fold increase in activity."
FT                   /evidence="ECO:0000269|PubMed:16385005"
FT   CONFLICT        1
FT                   /note="M -> MKL (in Ref. 2; AAL25087)"
FT                   /evidence="ECO:0000305"
FT   STRAND          5..12
FT                   /evidence="ECO:0007829|PDB:4ZXG"
FT   TURN            14..16
FT                   /evidence="ECO:0007829|PDB:4ZXG"
FT   HELIX           17..26
FT                   /evidence="ECO:0007829|PDB:4ZXG"
FT   STRAND          31..35
FT                   /evidence="ECO:0007829|PDB:4ZXG"
FT   STRAND          37..39
FT                   /evidence="ECO:0007829|PDB:4ZXG"
FT   HELIX           41..51
FT                   /evidence="ECO:0007829|PDB:4ZXG"
FT   STRAND          55..57
FT                   /evidence="ECO:0007829|PDB:4ZXG"
FT   STRAND          61..64
FT                   /evidence="ECO:0007829|PDB:4ZXG"
FT   STRAND          67..70
FT                   /evidence="ECO:0007829|PDB:4ZXG"
FT   HELIX           72..82
FT                   /evidence="ECO:0007829|PDB:4ZXG"
FT   HELIX           90..111
FT                   /evidence="ECO:0007829|PDB:4ZXG"
FT   TURN            115..118
FT                   /evidence="ECO:0007829|PDB:4ZXG"
FT   HELIX           120..126
FT                   /evidence="ECO:0007829|PDB:4ZXG"
FT   HELIX           128..141
FT                   /evidence="ECO:0007829|PDB:4ZXG"
FT   TURN            142..144
FT                   /evidence="ECO:0007829|PDB:1Q4J"
FT   HELIX           160..175
FT                   /evidence="ECO:0007829|PDB:4ZXG"
FT   TURN            179..182
FT                   /evidence="ECO:0007829|PDB:1OKT"
FT   HELIX           184..194
FT                   /evidence="ECO:0007829|PDB:4ZXG"
FT   HELIX           197..205
FT                   /evidence="ECO:0007829|PDB:4ZXG"
SQ   SEQUENCE   211 AA;  24789 MW;  EDC79583CFC9D751 CRC64;
     MGDNIVLYYF DARGKAELIR LIFAYLGIEY TDKRFGVNGD AFVEFKNFKK EKDTPFEQVP
     ILQIGDLILA QSQAIVRYLS KKYNICGESE LNEFYADMIF CGVQDIHYKF NNTNLFKQNE
     TTFLNEDLPK WSGYFEKLLK KNHTNNNNDK YYFVGNNLTY ADLAVFNLYD DIETKYPSSL
     KNFPLLKAHN EFISNLPNIK NYITNRKESV Y
//