2c3q: Difference between revisions
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[[Image:2c3q.gif|left|200px]] | [[Image:2c3q.gif|left|200px]] | ||
'''HUMAN GLUTATHIONE-S-TRANSFERASE T1-1 W234R MUTANT, COMPLEX WITH S-HEXYLGLUTATHIONE''' | {{Structure | ||
|PDB= 2c3q |SIZE=350|CAPTION= <scene name='initialview01'>2c3q</scene>, resolution 1.85Å | |||
|SITE= <scene name='pdbsite=AC1:Iod+Binding+Site+For+Chain+D'>AC1</scene> | |||
|LIGAND= <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene> and <scene name='pdbligand=GTX:S-HEXYLGLUTATHIONE'>GTX</scene> | |||
|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] | |||
|GENE= | |||
}} | |||
'''HUMAN GLUTATHIONE-S-TRANSFERASE T1-1 W234R MUTANT, COMPLEX WITH S-HEXYLGLUTATHIONE''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2C3Q is a [ | 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== | ||
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:// | 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]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''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
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| 2c3q, resolution 1.85Å | |||||||||||||
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| Sites: | AC1 | ||||||||||||
| Ligands: | IOD and GTX | ||||||||||||
| 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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