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|3qag, resolution 2.00Å ()|
|Gene:||GSTO2 (Homo sapiens)|
|Related:||3q18, 3q19, 1eem|
Human Glutathione Transferase O2 with glutathione -new crystal form
The reduction of dehydroascorbate (DHA) to ascorbic acid (AA) is a vital cellular function. The omega-class glutathione S-transferases (GSTs) catalyze several reductive reactions in cellular biochemistry, including DHA reduction. In humans, two isozymes (GSTO1-1 and GSTO2-2) with significant DHA reductase (DHAR) activity are found, sharing 64% sequence identity. While the activity of GSTO2-2 is higher, it is significantly more unstable in vitro. We report the first crystal structures of human GSTO2-2, stabilized through site-directed mutagenesis and determined at 1.9 A resolution in the presence and absence of glutathione (GSH). The structure of a human GSTO1-1 has been determined at 1.7 A resolution in complex with the reaction product AA, which unexpectedly binds in the G-site, where the glutamyl moiety of GSH binds. The structure suggests a similar mode of ascorbate binding in GSTO2-2. This is the first time that a non-GSH-based reaction product has been observed in the G-site of any GST. AA stacks against a conserved aromatic residue, F34 (equivalent to Y34 in GSTO2-2). Mutation of Y34 to alanine in GSTO2-2 eliminates DHAR activity. From these structures and other biochemical data, we propose a mechanism of substrate binding and catalysis of DHAR activity.
Structural Insights into the Dehydroascorbate Reductase Activity of Human Omega-Class Glutathione Transferases., Zhou H, Brock J, Liu D, Board PG, Oakley AJ, J Mol Biol. 2012 Apr 18. PMID:22522127
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
[GSTO2_HUMAN] Exhibits glutathione-dependent thiol transferase activity. Has high dehydroascorbate reductase activity and may contribute to the recycling of ascorbic acid. Participates in the biotransformation of inorganic arsenic and reduces monomethylarsonic acid (MMA).
About this Structure
- Zhou H, Brock J, Liu D, Board PG, Oakley AJ. Structural Insights into the Dehydroascorbate Reductase Activity of Human Omega-Class Glutathione Transferases. J Mol Biol. 2012 Apr 18. PMID:22522127 doi:10.1016/j.jmb.2012.04.014
- ↑ Schmuck EM, Board PG, Whitbread AK, Tetlow N, Cavanaugh JA, Blackburn AC, Masoumi A. Characterization of the monomethylarsonate reductase and dehydroascorbate reductase activities of Omega class glutathione transferase variants: implications for arsenic metabolism and the age-at-onset of Alzheimer's and Parkinson's diseases. Pharmacogenet Genomics. 2005 Jul;15(7):493-501. PMID:15970797