1q4j

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(New page: 200px<br /><applet load="1q4j" size="450" color="white" frame="true" align="right" spinBox="true" caption="1q4j, resolution 2.20&Aring;" /> '''Crystal Structure of...)
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[[Image:1q4j.jpg|left|200px]]<br /><applet load="1q4j" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1q4j, resolution 2.20&Aring;" />
 
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'''Crystal Structure of Pf-GST1 with its inhibitor s-hexyl-GSH'''<br />
 
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==Overview==
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==Crystal Structure of Pf-GST1 with its inhibitor s-hexyl-GSH==
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The parasite Plasmodium falciparum causes malaria tropica, the most, prevailing parasitic disease worldwide, with 300-500 million infections, and 1.5-2.7 million deaths/year. The emergence of strains resistant to, drugs used for prophylaxis and treatment and no vaccine available makes, the structural analysis of potential drug targets essential. For that, reason, we analyzed the three-dimensional structure of the glutathione, S-transferase from P. falciparum (Pf-GST1) in the apoform and in complex, with its inhibitor S-hexyl-glutathione. The structures have been analyzed, to 2.6 and 2.2 A, respectively. Pf-GST1 shares several structural features, with the Mu-type GSTs and is therefore closely related to this class, even, though alignments with its members display low sequence identities in the, range of 20-33%. Upon S-hexyl-glutathione binding, the overall structure, and the glutathione-binding site (G-site) remain almost unchanged with the, exception of the flexible C terminus. The detailed comparison of the, parasitic enzyme with the human host Mu-class enzyme reveals that, although the overall structure is homologue, the shape of the hydrophobic, binding pocket (H-site) differs substantially. In the human enzyme, it is, shielded from one side by the large Mu-loop, whereas in Pf-GST1 the, Mu-loop is truncated and the space to recognize and bind voluminous, substrates is extended. This structural feature can be exploited to, support the design of specific and parasite-selective inhibitors.
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<StructureSection load='1q4j' size='340' side='right'caption='[[1q4j]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1q4j]] 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=1Q4J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Q4J FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTX:S-HEXYLGLUTATHIONE'>GTX</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1q4j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q4j OCA], [https://pdbe.org/1q4j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1q4j RCSB], [https://www.ebi.ac.uk/pdbsum/1q4j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1q4j ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/q4/1q4j_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1q4j ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1Q4J is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum] with GTX as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1Q4J OCA].
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*[[Glutathione S-transferase 3D structures|Glutathione S-transferase 3D structures]]
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== References ==
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==Reference==
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<references/>
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Native and inhibited structure of a Mu class-related glutathione S-transferase from Plasmodium falciparum., Perbandt M, Burmeister C, Walter RD, Betzel C, Liebau E, J Biol Chem. 2004 Jan 9;279(2):1336-42. Epub 2003 Sep 12. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12972411 12972411]
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Plasmodium falciparum]]
[[Category: Plasmodium falciparum]]
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[[Category: Single protein]]
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[[Category: Betzel C]]
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[[Category: Betzel, C.]]
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[[Category: Liebau E]]
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[[Category: Liebau, E.]]
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[[Category: Perbandt M]]
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[[Category: Perbandt, M.]]
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[[Category: GTX]]
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[[Category: transferase]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 00:22:58 2007''
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Current revision

Crystal Structure of Pf-GST1 with its inhibitor s-hexyl-GSH

PDB ID 1q4j

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