2c3q
From Proteopedia
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|PDB= 2c3q |SIZE=350|CAPTION= <scene name='initialview01'>2c3q</scene>, resolution 1.85Å | |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> | |SITE= <scene name='pdbsite=AC1:Iod+Binding+Site+For+Chain+D'>AC1</scene> | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=GTX:S-HEXYLGLUTATHIONE'>GTX</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2c3q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c3q OCA], [http://www.ebi.ac.uk/pdbsum/2c3q PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2c3q RCSB]</span> | ||
}} | }} | ||
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[[Category: Shokeer, A.]] | [[Category: Shokeer, A.]] | ||
[[Category: Tars, K.]] | [[Category: Tars, K.]] | ||
| - | [[Category: GTX]] | ||
| - | [[Category: IOD]] | ||
[[Category: glutathione]] | [[Category: glutathione]] | ||
[[Category: glutathione transferase]] | [[Category: glutathione transferase]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:15:51 2008'' |
Revision as of 23:15, 30 March 2008
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| , resolution 1.85Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | , | ||||||
| Activity: | Glutathione transferase, with EC number 2.5.1.18 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| 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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