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[[Image:2c3t.gif|left|200px]]
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{{STRUCTURE_2c3t|  PDB=2c3t  |  SCENE=  }}
'''HUMAN GLUTATHIONE-S-TRANSFERASE T1-1, W234R MUTANT, APO FORM'''


==Human glutathione-S-transferase T1-1, W234R mutant, apo form==
<StructureSection load='2c3t' size='340' side='right'caption='[[2c3t]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2c3t]] is a 4 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=2C3T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2C3T 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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2c3t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c3t OCA], [https://pdbe.org/2c3t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2c3t RCSB], [https://www.ebi.ac.uk/pdbsum/2c3t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2c3t ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GSTT1_HUMAN GSTT1_HUMAN] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Acts on 1,2-epoxy-3-(4-nitrophenoxy)propane, phenethylisothiocyanate 4-nitrobenzyl chloride and 4-nitrophenethyl bromide. Displays glutathione peroxidase activity with cumene hydroperoxide.<ref>PMID:16298388</ref> <ref>PMID:20097269</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/c3/2c3t_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=2c3t ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The crystal structures of wild-type human theta class glutathione-S-transferase (GST) T1-1 and its W234R mutant, where Trp234 was replaced by Arg, were solved both in the presence and absence of S-hexyl-glutathione. The W234R mutant was of interest due to its previously observed enhanced catalytic activity compared to the wild-type enzyme. GST T1-1 from rat and mouse naturally contain Arg in position 234, with correspondingly high catalytic efficiency. The overall structure of GST T1-1 is similar to that of GST T2-2, as expected from their 53% sequence identity at the protein level. Wild-type GST T1-1 has the side-chain of Trp234 occupying a significant portion of the active site. This bulky residue prevents efficient binding of both glutathione and hydrophobic substrates through steric hindrance. The wild-type GST T1-1 crystal structure, obtained from co-crystallization experiments with glutathione and its derivatives, showed no electron density for the glutathione ligand. However, the structure of GST T1-1 mutant W234R showed clear electron density for S-hexyl-glutathione after co-crystallization. In contrast to Trp234 in the wild-type structure, the side-chain of Arg234 in the mutant does not occupy any part of the substrate-binding site. Instead, Arg234 is pointing in a different direction and, in addition, interacts with the carboxylate group of glutathione. These findings explain our earlier observation that the W234R mutant has a markedly improved catalytic activity with most substrates tested to date compared to the wild-type enzyme. GST T1-1 catalyzes detoxication reactions as well as reactions that result in toxic products, and our findings therefore suggest that humans have gained an evolutionary advantage by a partially disabled active site.


==Overview==
Structural basis of the suppressed catalytic activity of wild-type human glutathione transferase T1-1 compared to its W234R mutant.,Tars K, Larsson AK, Shokeer A, Olin B, Mannervik B, Kleywegt GJ J Mol Biol. 2006 Jan 6;355(1):96-105. Epub 2005 Nov 8. PMID:16298388<ref>PMID:16298388</ref>
The crystal structures of wild-type human theta class glutathione-S-transferase (GST) T1-1 and its W234R mutant, where Trp234 was replaced by Arg, were solved both in the presence and absence of S-hexyl-glutathione. The W234R mutant was of interest due to its previously observed enhanced catalytic activity compared to the wild-type enzyme. GST T1-1 from rat and mouse naturally contain Arg in position 234, with correspondingly high catalytic efficiency. The overall structure of GST T1-1 is similar to that of GST T2-2, as expected from their 53% sequence identity at the protein level. Wild-type GST T1-1 has the side-chain of Trp234 occupying a significant portion of the active site. This bulky residue prevents efficient binding of both glutathione and hydrophobic substrates through steric hindrance. The wild-type GST T1-1 crystal structure, obtained from co-crystallization experiments with glutathione and its derivatives, showed no electron density for the glutathione ligand. However, the structure of GST T1-1 mutant W234R showed clear electron density for S-hexyl-glutathione after co-crystallization. In contrast to Trp234 in the wild-type structure, the side-chain of Arg234 in the mutant does not occupy any part of the substrate-binding site. Instead, Arg234 is pointing in a different direction and, in addition, interacts with the carboxylate group of glutathione. These findings explain our earlier observation that the W234R mutant has a markedly improved catalytic activity with most substrates tested to date compared to the wild-type enzyme. GST T1-1 catalyzes detoxication reactions as well as reactions that result in toxic products, and our findings therefore suggest that humans have gained an evolutionary advantage by a partially disabled active site.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
2C3T is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2C3T OCA].
</div>
<div class="pdbe-citations 2c3t" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Structural basis of the suppressed catalytic activity of wild-type human glutathione transferase T1-1 compared to its W234R mutant., Tars K, Larsson AK, Shokeer A, Olin B, Mannervik B, Kleywegt GJ, J Mol Biol. 2006 Jan 6;355(1):96-105. Epub 2005 Nov 8. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16298388 16298388]
*[[Glutathione S-transferase 3D structures|Glutathione S-transferase 3D structures]]
[[Category: Glutathione transferase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Kleywegt, G J.]]
[[Category: Kleywegt GJ]]
[[Category: Larsson, A K.]]
[[Category: Larsson A-K]]
[[Category: Mannervik, B.]]
[[Category: Mannervik B]]
[[Category: Olin, B.]]
[[Category: Olin B]]
[[Category: Shokeer, A.]]
[[Category: Shokeer A]]
[[Category: Tars, K.]]
[[Category: Tars K]]
[[Category: Glutathione]]
[[Category: Glutathione transferase]]
[[Category: Polymorphism]]
[[Category: T1-1]]
[[Category: Transferase]]
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Retrieved from "https://proteopedia.org/2c3t"