4IS0

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

4IS0 の概要

• エントリーDOI: 10.2210/pdb4is0/pdb
• 関連するPDBエントリー: 1EEM 1GTA 2GSQ 3Q19 3VLN
• 分子名称: Glutathione S-transferase omega-1, SULFATE ION, OXIDIZED GLUTATHIONE DISULFIDE, ... (6 entities in total)
• 機能のキーワード: gst fold, oxidoreductase, ligand-binding, cytosol, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm, cytosol : P78417
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 28997.24

構造登録者

Brock, J.,Oakley, A.J. (登録日: 2013-01-15, 公開日: 2013-04-24, 最終更新日: 2024-11-06)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.721 Å)