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| | ==Ligandin binding site of PfGST== | | ==Ligandin binding site of PfGST== |
| - | <StructureSection load='4zxg' size='340' side='right' caption='[[4zxg]], [[Resolution|resolution]] 1.70Å' scene=''> | + | <StructureSection load='4zxg' size='340' side='right'caption='[[4zxg]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4zxg]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Plafa Plafa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZXG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZXG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4zxg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZXG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZXG FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GST ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5833 PLAFA])</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4zxg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zxg OCA], [https://pdbe.org/4zxg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zxg RCSB], [https://www.ebi.ac.uk/pdbsum/4zxg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zxg ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glutathione_transferase Glutathione transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.18 2.5.1.18] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4zxg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zxg OCA], [http://pdbe.org/4zxg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zxg RCSB], [http://www.ebi.ac.uk/pdbsum/4zxg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zxg ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GST_PLAFA GST_PLAFA]] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. May also function as a storage protein or ligandin for parasitotoxic ferriprotoporphyrin IX (hemin).<ref>PMID:12108547</ref> <ref>PMID:12387854</ref> <ref>PMID:16385005</ref> | + | [https://www.uniprot.org/uniprot/GST_PLAF7 GST_PLAF7] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. May also function as a storage protein or ligandin for parasitotoxic ferriprotoporphyrin IX (hemin).<ref>PMID:12108547</ref> <ref>PMID:12387854</ref> <ref>PMID:16385005</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Glutathione S-transferase|Glutathione S-transferase]] | + | *[[Glutathione S-transferase 3D structures|Glutathione S-transferase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Glutathione transferase]] | + | [[Category: Large Structures]] |
| - | [[Category: Plafa]]
| + | |
| - | [[Category: Betzel, C]]
| + | |
| - | [[Category: Eberle, R]]
| + | |
| - | [[Category: Perbandt, M]]
| + | |
| - | [[Category: Gst]]
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| - | [[Category: Hemin]]
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| | [[Category: Plasmodium falciparum]] | | [[Category: Plasmodium falciparum]] |
| - | [[Category: Transferase]] | + | [[Category: Betzel C]] |
| | + | [[Category: Eberle R]] |
| | + | [[Category: Perbandt M]] |
| Structural highlights
Function
GST_PLAF7 Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. May also function as a storage protein or ligandin for parasitotoxic ferriprotoporphyrin IX (hemin).[1] [2] [3]
Publication Abstract from PubMed
Protection from oxidative stress and efficient redox regulation are essential for malarial parasites which have to grow and multiply rapidly in pro-oxidant rich environments. Therefore, redox active proteins currently belong to the most attractive antimalarial drug targets. The glutathione S -transferase from Plasmodium falciparum (PfGST) is a redox active protein displaying a peculiar dimer-tetramer transition that causes full enzyme-inactivation. This distinct structural feature is absent in mammalian GST isoenzyme counterparts. A flexible loop between residues 113-119 has been reported to be necessary for this tetramerization process. However, here we present structural data of a modified PfGST lacking loop 113-119 at 1.9 A resolution. Our results clearly show that this loop is not essential for the formation of stable tetramers. Moreover we present for the first time the structures of both, the inactive and tetrameric state at 1.7 A and the active dimeric state in complex with reduced glutathione at 2.4 A resolution. Surprisingly, the structure of the inactive tetrameric state reveals a novel non-substrate binding-site occupied by a 2-(N-morpholino) ethane sulfonic acid (MES) molecule in each monomer. Although it is known that the PfGST has the ability to bind lipophilic anionic ligands, the location of the PfGST ligand-binding site remained unclear up to now.
High resolution structures of Plasmodium falciparum GST complexes provide novel insights into the dimer-tetramer transition and a novel ligand-binding site.,Perbandt M, Eberle R, Fischer-Riepe L, Liebau E, Betzel C J Struct Biol. 2015 Jun 10. pii: S1047-8477(15)30012-5. doi:, 10.1016/j.jsb.2015.06.008. PMID:26072058[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Harwaldt P, Rahlfs S, Becker K. Glutathione S-transferase of the malarial parasite Plasmodium falciparum: characterization of a potential drug target. Biol Chem. 2002 May;383(5):821-30. PMID:12108547 doi:http://dx.doi.org/10.1515/BC.2002.086
- ↑ Liebau E, Bergmann B, Campbell AM, Teesdale-Spittle P, Brophy PM, Luersen K, Walter RD. The glutathione S-transferase from Plasmodium falciparum. Mol Biochem Parasitol. 2002 Sep-Oct;124(1-2):85-90. PMID:12387854
- ↑ Hiller N, Fritz-Wolf K, Deponte M, Wende W, Zimmermann H, Becker K. Plasmodium falciparum glutathione S-transferase--structural and mechanistic studies on ligand binding and enzyme inhibition. Protein Sci. 2006 Feb;15(2):281-9. Epub 2005 Dec 29. PMID:16385005 doi:10.1110/ps.051891106
- ↑ Perbandt M, Eberle R, Fischer-Riepe L, Liebau E, Betzel C. High resolution structures of Plasmodium falciparum GST complexes provide novel insights into the dimer-tetramer transition and a novel ligand-binding site. J Struct Biol. 2015 Jun 10. pii: S1047-8477(15)30012-5. doi:, 10.1016/j.jsb.2015.06.008. PMID:26072058 doi:http://dx.doi.org/10.1016/j.jsb.2015.06.008
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