4IS0

Structural Insights into Omega-Class Glutathione Transferases: A Snapshot of Enzyme Reduction and Identification of the Non-Catalytic Ligandin Site.

Summary for 4IS0

• Entry DOI: 10.2210/pdb4is0/pdb
• Related: 1EEM 1GTA 2GSQ 3Q19 3VLN
• Descriptor: Glutathione S-transferase omega-1, SULFATE ION, OXIDIZED GLUTATHIONE DISULFIDE, ... (6 entities in total)
• Functional Keywords: gst fold, oxidoreductase, ligand-binding, cytosol, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm, cytosol : P78417
• Total number of polymer chains: 1
• Total formula weight: 28997.24

Authors

Brock, J.,Oakley, A.J. (deposition date: 2013-01-15, release date: 2013-04-24, Last modification date: 2024-11-06)

Primary citation

Brock, J.,Board, P.G.,Oakley, A.J.
Structural insights into omega-class glutathione transferases: a snapshot of enzyme reduction and identification of a non-catalytic ligandin site.
Plos One, 8:e60324-e60324, 2013

PubMed Abstract: Glutathione transferases (GSTs) are dimeric enzymes containing one active-site per monomer. The omega-class GSTs (hGSTO1-1 and hGSTO2-2 in humans) are homodimeric and carry out a range of reactions including the glutathione-dependant reduction of a range of compounds and the reduction of S-(phenacyl)glutathiones to acetophenones. Both types of reaction result in the formation of a mixed-disulfide of the enzyme with glutathione through the catalytic cysteine (C32). Recycling of the enzyme utilizes a second glutathione molecule and results in oxidized glutathione (GSSG) release. The crystal structure of an active-site mutant (C32A) of the hGSTO1-1 isozyme in complex with GSSG provides a snapshot of the enzyme in the process of regeneration. GSSG occupies both the G (GSH-binding) and H (hydrophobic-binding) sites and causes re-arrangement of some H-site residues. In the same structure we demonstrate the existence of a novel "ligandin" binding site deep within in the dimer interface of this enzyme, containing S-(4-nitrophenacyl)glutathione, an isozyme-specific substrate for hGSTO1-1. The ligandin site, conserved in Omega class GSTs from a range of species, is hydrophobic in nature and may represent the binding location for tocopherol esters that are uncompetitive hGSTO1-1 inhibitors.

PubMed: 23593192
DOI: 10.1371/journal.pone.0060324

Experimental method

X-RAY DIFFRACTION (1.721 Å)