2c3q

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[[Image:2c3q.gif|left|200px]]<br /><applet load="2c3q" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:2c3q.gif|left|200px]]
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caption="2c3q, resolution 1.85&Aring;" />
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'''HUMAN GLUTATHIONE-S-TRANSFERASE T1-1 W234R MUTANT, COMPLEX WITH S-HEXYLGLUTATHIONE'''<br />
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{{Structure
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|PDB= 2c3q |SIZE=350|CAPTION= <scene name='initialview01'>2c3q</scene>, resolution 1.85&Aring;
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|SITE= <scene name='pdbsite=AC1:Iod+Binding+Site+For+Chain+D'>AC1</scene>
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|LIGAND= <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene> and <scene name='pdbligand=GTX:S-HEXYLGLUTATHIONE'>GTX</scene>
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|ACTIVITY= [http://en.wikipedia.org/wiki/Glutathione_transferase Glutathione transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.18 2.5.1.18]
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|GENE=
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}}
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'''HUMAN GLUTATHIONE-S-TRANSFERASE T1-1 W234R MUTANT, COMPLEX WITH S-HEXYLGLUTATHIONE'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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2C3Q is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=IOD:'>IOD</scene> and <scene name='pdbligand=GTX:'>GTX</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Glutathione_transferase Glutathione transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.18 2.5.1.18] Known structural/functional Site: <scene name='pdbsite=AC1:Iod+Binding+Site+For+Chain+D'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2C3Q OCA].
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2C3Q 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=2C3Q OCA].
==Reference==
==Reference==
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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://ispc.weizmann.ac.il//pmbin/getpm?pmid=16298388 16298388]
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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]
[[Category: Glutathione transferase]]
[[Category: Glutathione transferase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: transferase]]
[[Category: transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:44:35 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 16:10:23 2008''

Revision as of 14:10, 20 March 2008

Image:2c3q.gif


PDB ID 2c3q

Drag the structure with the mouse to rotate
, resolution 1.85Å
Sites:
Ligands: and
Activity: Glutathione transferase, with EC number 2.5.1.18
Coordinates: save as pdb, mmCIF, xml



HUMAN GLUTATHIONE-S-TRANSFERASE T1-1 W234R MUTANT, COMPLEX WITH S-HEXYLGLUTATHIONE


Overview

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

2C3Q is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

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

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