View source for 1tdi


==Crystal Structure of hGSTA3-3 in Complex with Glutathione==
<StructureSection load='1tdi' size='340' side='right'caption='[[1tdi]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1tdi]] 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=1TDI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TDI 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=GSH:GLUTATHIONE'>GSH</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=1tdi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tdi OCA], [https://pdbe.org/1tdi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1tdi RCSB], [https://www.ebi.ac.uk/pdbsum/1tdi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1tdi ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GSTA3_HUMAN GSTA3_HUMAN] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Catalyzes isomerization reactions that contribute to the biosynthesis of steroid hormones. Efficiently catalyze obligatory double-bond isomerizations of delta(5)-androstene-3,17-dione and delta(5)-pregnene-3,20-dione, precursors to testosterone and progesterone, respectively.<ref>PMID:15595823</ref> <ref>PMID:20083122</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/td/1tdi_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=1tdi ConSurf].
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== Publication Abstract from PubMed ==
The crystal structure of human class alpha glutathione (GSH) S-transferase A3-3 (hGSTA3-3) in complex with GSH was determined at 2.4 A. Despite considerable amino acid sequence identity with other human class alpha GSTs (e.g., hGSTA1-1), hGSTA3-3 is unique due to its exceptionally high steroid double bond isomerase activity for the transformation of Delta(5)-androstene-3,17-dione (Delta(5)-AD) to Delta(4)-androstene-3,17-dione. A comparative analysis of the active centers of hGSTA1-1 and hGSTA3-3 reveals that residues in positions 12 and 208 may contribute to their disparate isomerase activity toward Delta(5)-AD. Substitution of these two residues of hGSTA3-3 with the corresponding residues in hGSTA1-1 followed by kinetic characterization of the wild-type and the mutant enzymes supported this prediction. On the basis of our model of the hGSTA3-3.GSH.Delta(5)-AD ternary complex and available biochemical data, we propose that the thiolate group of deprotonated GSH (GS(-)) serves as a base to initiate the reaction by accepting a proton from the steroid and the nonionized hydroxyl group of catalytic residue Y9 (HO-Y9) functions as part of a proton-conducting wire to transfer a proton back to the steroid. Residue R15 may function to stabilize the deprotonated thiolate group of GSH (GS(-)), and a GSH-bound water molecule may donate a hydrogen bond to the 3-keto group of Delta(5)-AD and thus help the thiolate of GS(-) to initiate the proton transfer and the subsequent stabilization of the reaction intermediate.

Crystal structure of human glutathione S-transferase A3-3 and mechanistic implications for its high steroid isomerase activity.,Gu Y, Guo J, Pal A, Pan SS, Zimniak P, Singh SV, Ji X Biochemistry. 2004 Dec 21;43(50):15673-9. PMID:15595823<ref>PMID:15595823</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 1tdi" 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: Gu Y]]
[[Category: Guo J]]
[[Category: Ji X]]
[[Category: Pal A]]
[[Category: Pan SS]]
[[Category: Singh SV]]
[[Category: Zimniak P]]