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| - | [[Image:2c3t.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_2c3t| PDB=2c3t | SCENE= }} | | {{STRUCTURE_2c3t| PDB=2c3t | SCENE= }} |
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| - | '''HUMAN GLUTATHIONE-S-TRANSFERASE T1-1, W234R MUTANT, APO FORM'''
| + | ===HUMAN GLUTATHIONE-S-TRANSFERASE T1-1, W234R MUTANT, APO FORM=== |
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| - | ==Overview==
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| - | 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. | + | The line below this paragraph, {{ABSTRACT_PUBMED_16298388}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 16298388 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_16298388}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: T1-1]] | | [[Category: T1-1]] |
| | [[Category: Transferase]] | | [[Category: Transferase]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 21:12:27 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 20:12:40 2008'' |
Revision as of 17:12, 27 July 2008
Template:STRUCTURE 2c3t
HUMAN GLUTATHIONE-S-TRANSFERASE T1-1, W234R MUTANT, APO FORM
Template:ABSTRACT PUBMED 16298388
About this Structure
2C3T 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
Page seeded by OCA on Sun Jul 27 20:12:40 2008
