3Q19

Human Glutathione Transferase O2

Summary for 3Q19

• Entry DOI: 10.2210/pdb3q19/pdb
• Related: 1EEM 3Q18
• Descriptor: Glutathione S-transferase omega-2, GLUTATHIONE, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: glutathione transferase, gst, dehydroascorbate reductase, transferase, reductase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 56225.35

Authors

Zhou, H.,Board, P.G.,Oakley, A.J. (deposition date: 2010-12-16, release date: 2012-01-25, Last modification date: 2023-11-01)

Primary citation

Zhou, H.,Brock, J.,Liu, D.,Board, P.G.,Oakley, A.J.
Structural insights into the dehydroascorbate reductase activity of human omega-class glutathione transferases.
J.Mol.Biol., 420:190-203, 2012

PubMed Abstract: The reduction of dehydroascorbate (DHA) to ascorbic acid (AA) is a vital cellular function. The omega-class glutathione 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 Å resolution in the presence and absence of glutathione (GSH). The structure of a human GSTO1-1 has been determined at 1.7 Å 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.

PubMed: 22522127
DOI: 10.1016/j.jmb.2012.04.014

Experimental method

X-RAY DIFFRACTION (1.9 Å)