View source for 22gs


==HUMAN GLUTATHIONE S-TRANSFERASE P1-1 Y49F MUTANT==
<StructureSection load='22gs' size='340' side='right'caption='[[22gs]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[22gs]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=22GS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=22GS 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]] 1.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</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=22gs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=22gs OCA], [https://pdbe.org/22gs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=22gs RCSB], [https://www.ebi.ac.uk/pdbsum/22gs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=22gs ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GSTP1_HUMAN GSTP1_HUMAN] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration.<ref>PMID:21668448</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/2g/22gs_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=22gs ConSurf].
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== Publication Abstract from PubMed ==
The thermodynamics of binding of both the substrate glutathione (GSH) and the competitive inhibitor S-hexylglutathione to the mutant Y49F of human glutathione S-transferase (hGST P1-1), a key residue at the dimer interface, has been investigated by isothermal titration calorimetry and fluorescence spectroscopy. Calorimetric measurements indicated that the binding of these ligands to both the Y49F mutant and wild-type enzyme is enthalpically favorable and entropically unfavorable over the temperature range studied. The affinity of these ligands for the Y49F mutant is lower than those for the wild-type enzyme due mainly to an entropy change. Therefore, the thermodynamic effect of this mutation is to decrease the entropy loss due to binding. Calorimetric titrations in several buffers with different ionization heat amounts indicate a release of protons when the mutant binds GSH, whereas protons are taken up in binding S-hexylglutathione at pH 6.5. This suggests that the thiol group of GSH releases protons to buffer media during binding and a group with low pKa (such as Asp98) is responsible for the uptake of protons. The temperature dependence of the free energy of binding, DeltaG0, is weak because of the enthalpy-entropy compensation caused by a large heat capacity change. The heat capacity change is -199.5 +/- 26.9 cal K-1 mol-1 for GSH binding and -333.6 +/- 28.8 cal K-1 mol-1 for S-hexylglutathione binding. The thermodynamic parameters are consistent with the mutation Tyr49 --&gt; Phe, producing a slight conformational change in the active site.

Thermodynamic description of the effect of the mutation Y49F on human glutathione transferase P1-1 in binding with glutathione and the inhibitor S-hexylglutathione.,Ortiz-Salmeron E, Nuccetelli M, Oakley AJ, Parker MW, Lo Bello M, Garcia-Fuentes L J Biol Chem. 2003 Nov 21;278(47):46938-48. Epub 2003 Aug 23. PMID:12937169<ref>PMID:12937169</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 22gs" style="background-color:#fffaf0;"></div>

==See Also==
*[[Glutathione S-transferase 3D structures|Glutathione S-transferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Oakley AJ]]