8GSS

Human glutathione S-transferase P1-1, complex with glutathione

8GSS の概要

• エントリーDOI: 10.2210/pdb8gss/pdb
• 分子名称: GLUTATHIONE S-TRANSFERASE P1-1, SULFATE ION, GLUTATHIONE, ... (5 entities in total)
• 機能のキーワード: transferase, glutathione
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 71244.28

構造登録者

Oakley, A.,Parker, M. (登録日: 1997-08-14, 公開日: 1998-09-16, 最終更新日: 2023-08-09)

主引用文献

Oakley, A.J.,Bello, M.L.,Battistoni, A.,Ricci, G.,Rossjohn, J.,Villar, H.O.,Parker, M.W.
The structures of human glutathione transferase P1-1 in complex with glutathione and various inhibitors at high resolution.
J.Mol.Biol., 274:84-100, 1997

PubMed Abstract: The human pi-class glutathione S-transferase (hGST P1-1) is a target for structure-based inhibitor design with the aim of developing drugs that could be used as adjuvants in chemotherapeutic treatment. Here we present seven crystal structures of the enzyme in complex with substrate (glutathione) and two inhibitors (S-hexyl glutathione and gamma-glutamyl- (S-benzyl)cysteinyl-D-phenylglycine). The binding of the modified glutathione inhibitor, gamma-glutamyl-(S-benzyl)cysteinyl-D-phenylglycine, has been characterized with the phenyl group stacking against the benzyl moiety of the inhibitor and making interactions with the active-site residues Phe8 and Trp38. The structure provides an explanation as to why this compound inhibits the pi-class GST much better than the other GST classes. The structure of the enzyme in complex with glutathione has been determined to high resolution (1.9 to 2.2 A) in three different crystal forms and at two different temperatures (100 and 288 K). In one crystal form, the direct hydrogen-bonding interaction between the hydroxyl group of Tyr7, a residue involved in catalysis, and the thiol group of the substrate, glutathione, is broken and replaced by a water molecule that mediates the interaction. The hydrogen-bonding partner of the hydroxyl group of Tyr108, another residue implicated in the catalysis, is space-group dependent. A high-resolution (2.0 A) structure of the enzyme in complex with S-hexyl glutathione in a new crystal form is presented. The enzyme-inhibitor complexes show that the binding of ligand into the electrophilic binding site does not lead to any conformational changes of the protein.

PubMed: 9398518
DOI: 10.1006/jmbi.1997.1364

実験手法

X-RAY DIFFRACTION (1.9 Å)