2C4J

Human glutathione-S-transferase M2-2 T210S mutant in complex with glutathione-styrene oxide conjugate

2C4J の概要

• エントリーDOI: 10.2210/pdb2c4j/pdb
• 関連するPDBエントリー: 1HNA 1HNB 1HNC 1XW5 1YKC 2AB6 2GTU 3GTU
• 分子名称: GLUTATHIONE S-TRANSFERASE MU 2, L-GAMMA-GLUTAMYL-S-[(2S)-2-HYDROXY-2-PHENYLETHYL]-L-CYSTEINYLGLYCINE (3 entities in total)
• 機能のキーワード: glutathione, glutathione transferase, transferase, m2-2, multigene family
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 104760.40

構造登録者

Tars, K.,Andersson, M.,Ivarsson, Y.,Olin, B.,Mannervik, B. (登録日: 2005-10-20, 公開日: 2005-10-26, 最終更新日: 2023-12-13)

主引用文献

Norrgard, M.A.,Ivarsson, Y.,Tars, K.,Mannervik, B.
Alternative Mutations of a Positively Selected Residue Elicit Gain or Loss of Functionalities in Enzyme Evolution.
Proc.Natl.Acad.Sci.USA, 103:4876-, 2006

PubMed Abstract: All molecular species in an organism are connected physically and functionally to other molecules. In evolving systems, it is not obvious to what extent functional properties of a protein can change to selective advantage and leave intact favorable traits previously acquired. This uncertainty has particular significance in the evolution of novel pathways for detoxication, because an organism challenged with new xenobiotics in the environment may still require biotransformation of previously encountered toxins. Positive selection has been proposed as an evolutionary mechanism for facile adaptive responses of proteins to changing conditions. Here, we show, by saturation mutagenesis, that mutations of a hypervariable residue in human glutathione transferase M2-2 can differentially change the enzyme's substrate-activity profile with alternative substrates and, furthermore, enable or disable dissimilar chemical reactions. Crystal structures demonstrate that activity with epoxides is enabled through removal of steric hindrance from a methyl group, whereas activities with an orthoquinone and a nitroso donor are maintained in the variant enzymes. Given the diversity of cellular activities in which a single protein can be engaged, the selective transmutation of functional properties has general significance in molecular evolution.

PubMed: 16549767
DOI: 10.1073/PNAS.0600849103

実験手法

X-RAY DIFFRACTION (1.35 Å)