2c3t
From Proteopedia
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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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[[Category: Shokeer, A.]] | [[Category: Shokeer, A.]] | ||
[[Category: Tars, K.]] | [[Category: Tars, K.]] | ||
| - | [[Category: | + | [[Category: Glutathione]] |
| - | [[Category: | + | [[Category: Glutathione transferase]] |
| - | [[Category: | + | [[Category: Polymorphism]] |
| - | [[Category: | + | [[Category: T1-1]] |
| - | [[Category: | + | [[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 | + | |
Revision as of 18:12, 3 May 2008
HUMAN GLUTATHIONE-S-TRANSFERASE T1-1, W234R MUTANT, APO FORM
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
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 Sat May 3 21:12:27 2008
