2WJU

Glutathione transferase A2-2 in complex with glutathione

「2VCR」から置き換えられました

2WJU の概要

• エントリーDOI: 10.2210/pdb2wju/pdb
• 関連するPDBエントリー: 1AGS 2VCT
• 分子名称: GLUTATHIONE-S-TRANSFERASE A2-2, GLUTATHIONE (3 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: 8
• 化学式量合計: 208178.63

構造登録者

Tars, K.,Olin, B.,Mannervik, B. (登録日: 2009-05-29, 公開日: 2009-06-09, 最終更新日: 2023-12-13)

主引用文献

Tars, K.,Olin, B.,Mannervik, B.
Structural Basis for Featuring of Steroid Isomerase Activity in Alpha Class Glutathione Transferases.
J.Mol.Biol., 397:332-, 2010

PubMed Abstract: Glutathione transferases (GSTs) are abundant enzymes catalyzing the conjugation of hydrophobic toxic substrates with glutathione. In addition to detoxication, human GST A3-3 displays prominent steroid double-bond isomerase activity; e.g. transforming Delta(5)-androstene-3-17-dione into Delta(4)-androstene-3-17-dione (AD). This chemical transformation is a crucial step in the biosynthesis of steroids, such as testosterone and progesterone. In contrast to GST A3-3, the homologous GST A2-2 does not show significant steroid isomerase activity. We have solved the 3D structures of human GSTs A2-2 and A3-3 in complex with AD. In the GST A3-3 crystal structure, AD was bound in an orientation suitable for the glutathione (GSH)-mediated catalysis to occur. In GST A2-2, however, AD was bound in a completely different orientation with its reactive double bond distant from the GSH-binding site. The structures illustrate how a few amino acid substitutions in the active site spectacularly alter the binding mode of the steroid substrate in relation to the conserved catalytic groups and an essentially fixed polypeptide chain conformation. Furthermore, AD did not bind to the GST A2-2-GSH complex. Altogether, these results provide a first-time structural insight into the steroid isomerase activity of any GST and explain the 5000-fold difference in catalytic efficiency between GSTs A2-2 and A3-3. More generally, the structures illustrate how dramatic diversification of functional properties can arise via minimal structural alterations. We suggest a novel structure-based mechanism of the steroid isomerization reaction.

PubMed: 20083122
DOI: 10.1016/J.JMB.2010.01.023

実験手法

X-RAY DIFFRACTION (2.3 Å)