View source for 2aaw


==Studies on ligand binding and enzyme inhibition of Plasmodium falciparum glutathione S-transferase==
<StructureSection load='2aaw' size='340' side='right'caption='[[2aaw]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2aaw]] 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=2AAW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AAW FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DTL:L-TREITOL'>DTL</scene>, <scene name='pdbligand=GTX:S-HEXYLGLUTATHIONE'>GTX</scene>, <scene name='pdbligand=P33:3,6,9,12,15,18-HEXAOXAICOSANE-1,20-DIOL'>P33</scene></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=2aaw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aaw OCA], [https://pdbe.org/2aaw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2aaw RCSB], [https://www.ebi.ac.uk/pdbsum/2aaw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2aaw ProSAT]</span></td></tr>
</table>
== Function ==
[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> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/aa/2aaw_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2aaw ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Glutathione S-transferase of the malarial parasite Plasmodium falciparum (PfGST) represents a novel class of GST isoenzymes. Since the architecture of the PfGST substrate binding site differs significantly from its human counterparts and there is only this one isoenzyme present in the parasite, PfGST is considered a highly attractive target for antimalarial drug development. Here we report the mechanistic, kinetic, and structural characterization of PfGST as well as its interaction with different ligands. Our data indicate that in solution PfGST is present as a tetramer that dissociates into dimers in the presence of glutathione (GSH). Fluorescence spectroscopy shows that in the presence of GSH GST serves as ligandin for parasitotoxic ferriprotoporphyrin IX with a high- and a low-affinity binding site. This is supported by a clear uncompetitive inhibition type. Site-directed mutagenesis studies demonstrate that neither Cys 86 nor Cys 101 contribute to the peroxidase activity of the enzyme, which is thus performed GSH-dependently at the active site. Tyr 9 is responsible for the deprotonation of GSH and Lys 15, but also Gln 71 are involved in GSH binding. We furthermore report the 2.4 A resolution X-ray structure of PfGST cocrystallized with the inhibitor S-hexylglutathione. In comparison with a previously reported structure obtained by crystal soaking, differences occur at the C-terminal end of helix alpha4 and at the S-hexylmoiety of the inhibitor. We furthermore show that, in contrast to previous reports, the antimalarial drug artemisinin is not metabolized by PfGST.

Plasmodium falciparum glutathione S-transferase--structural and mechanistic studies on ligand binding and enzyme inhibition.,Hiller N, Fritz-Wolf K, Deponte M, Wende W, Zimmermann H, Becker K Protein Sci. 2006 Feb;15(2):281-9. Epub 2005 Dec 29. PMID:16385005<ref>PMID:16385005</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2aaw" style="background-color:#fffaf0;"></div>

==See Also==
*[[Glutathione S-transferase 3D structures|Glutathione S-transferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Plasmodium falciparum]]
[[Category: Becker K]]
[[Category: Deponte M]]
[[Category: Fritz-Wolf K]]
[[Category: Hiller N]]
[[Category: Wende W]]
[[Category: Zimmermann H]]