2c3t

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2c3t, resolution 2.40Å ()
Activity: Glutathione transferase, with EC number 2.5.1.18
Related: 2c3n, 2c3q
Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml



Contents

HUMAN GLUTATHIONE-S-TRANSFERASE T1-1, W234R MUTANT, APO FORM

Publication Abstract from PubMed

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.

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

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

About this Structure

2c3t is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

See Also

Reference

  • Tars K, Larsson AK, Shokeer A, Olin B, Mannervik B, Kleywegt GJ. Structural basis of the suppressed catalytic activity of wild-type human glutathione transferase T1-1 compared to its W234R mutant. J Mol Biol. 2006 Jan 6;355(1):96-105. Epub 2005 Nov 8. PMID:16298388 doi:10.1016/j.jmb.2005.10.049

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