P450酵素とリドックスパートナーとの間の代替相互作用から生じる新しい反応と産物
Wei Zhang1, Yi Liu, Jinyong Yan
1CAS Key Laboratory of Biofuels, and Shandong Provincial Key Laboratory of Energy Genetics, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences , Qingdao, Shandong 266101, China.
Journal of the American Chemical Society
|February 14, 2014
まとめ
レドックスパートナーは,シトクロームP450酵素の活性を変えることができます. MycG (サイトクロームP450) は,自由還元酵素ドメインとの非自然なN-脱メチル化を触媒化したが,溶融したときには生理学的酸化のみであり,パートナー相互作用がP450触媒を調節することを明らかにした.
科学分野:
- バイオケミストリー バイオケミストリー
- 酵素学 酵素学とは
- 有機化学 オーガニック・ケミストリー
背景:
- サイトクロームP450酵素は,選択的なC-H機能化を含む様々な反応のための重要なバイオカタライストです.
- 代理レドックスパートナーは,酵素機能に影響を与えないと仮定して,P450の活性を再構成するために一般的に使用されます.
- P450の触媒的結果に対するリドックスパートナー選択の影響は,さらなる調査を必要とする分野です.
研究 の 目的:
- P450酵素MycG.の触媒活性と選択性に対する異なる酸化還元パートナー構成の影響を調査する.
- レドックスパートナーがP450反応結果に影響を与えないという一般的な仮定に異議を唱えるために.
- エンジニアリングされたタンパク質-タンパク質相互作用を通じてP450触媒を調節する可能性を調査する.
主な方法:
- MycG,P450モノオキシゲナーゼを,ミシナミシン基板で利用しました.
- 自由ロドコッカス還元酵素ドメイン (RhFRED) とエンジニアリングされたハイブリッド還元酵素 (RhFRED-Fdx) を使用して,再構成されたMycG活性.
- MycGの自由ドメインと融合された還元酵素ドメインの触媒的結果の比較.
主要な成果:
- MycGは,フリーRhFREDまたはRhFRED-Fdxと連携したときに,ミシナミシン基板の非自然なN-デメチル化を触媒化した.
- MycGがRhFREDまたはRhFRED-Fdxと融合すると,生理学的水酸化とエポキシデーションを独占的に媒介する.
- 還元酵素パートナーの物理的結合状態は,MycGの触媒的レパートリーを大幅に変化させた.
結論:
- レドックスパートナーとP450酵素の相互作用は,それらの触媒活性と選択性を深く調節することができます.
- エンジニアリングされたタンパク質とタンパク質の相互作用は,P450生物触媒を望ましい合成変換にリダイレクトするための新しい戦略を提供します.
- 発見は,P450媒介反応における被動的ファシリテーターとしての酸化還元パートナーの簡略的な見解に異議を唱える.
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