GST_PLAF7
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 03-AUG-2022, entry version 111.
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}; 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}.
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; 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; 5833.PF14_0187; -.
DR ChEMBL; CHEMBL1697656; -.
DR DrugBank; DB00608; Chloroquine.
DR DrugBank; DB01942; Formic acid.
DR DrugBank; DB04132; S-Hexylglutathione.
DR PRIDE; Q8ILQ7; -.
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 InParanoid; Q8ILQ7; -.
DR OMA; IKPKMIF; -.
DR PhylomeDB; Q8ILQ7; -.
DR BRENDA; 2.5.1.18; 4889.
DR Reactome; R-PFA-156590; Glutathione conjugation.
DR Reactome; R-PFA-189483; Heme degradation.
DR Reactome; R-PFA-2162123; Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
DR Reactome; R-PFA-3299685; Detoxification of Reactive Oxygen Species.
DR Reactome; R-PFA-6798695; Neutrophil degranulation.
DR Reactome; R-PFA-9748787; Azathioprine ADME.
DR Reactome; R-PFA-9753281; Paracetamol ADME.
DR EvolutionaryTrace; Q8ILQ7; -.
DR Proteomes; UP000001450; Chromosome 14.
DR GO; GO:0004364; F:glutathione transferase activity; IDA:GeneDB.
DR GO; GO:0006749; P:glutathione metabolic process; IBA:GO_Central.
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 Pfam; PF14497; GST_C_3; 1.
DR Pfam; PF02798; GST_N; 1.
DR SFLD; SFLDS00019; Glutathione_Transferase_(cytos; 1.
DR SUPFAM; SSF47616; SSF47616; 1.
DR SUPFAM; SSF52833; SSF52833; 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 20-
FT fold decrease in activity."
FT /evidence="ECO:0000269|PubMed:16385005"
FT MUTAGEN 71
FT /note="Q->E: 3-fold decrease in substrate affinity and 2-
FT 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
