Sirt5はNAD依存タンパク質であるライシン・デマロニラーゼとデスクシニラーゼである
Jintang Du1, Yeyun Zhou, Xiaoyang Su
1Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.
Science (New York, N.Y.)
|November 15, 2011
まとめ
哺乳類のサートゥインであるSirt5は,タンパク質からサクシニルおよびマロニル基を効率的に除去します. Sirt5によるこのタンパク質リジン改変の逆転は,新しい調節機構を vivo で示唆しています.
科学分野:
- バイオケミストリー バイオケミストリー
- 分子生物学は分子生物学である.
- 翻訳後の修正 翻訳後の修正
背景:
- シルトゥイン (Silent information regulator 2 proteins) は,重要な生物学的プロセスに関与するNAD+に依存した酵素である.
- 哺乳類には7つのサートゥイン (Sirt1-Sirt7) があり,Sirt4-Sirt7はデセチラゼの活性が限られているか全くない.
研究 の 目的:
- 脱エチル化を超えてSirt5の酵素活性を調査する.
- タンパク質リジンサクシニレーションとマロニレーションにおけるSirt5の役割を特定し,特徴づけること.
主な方法:
- Sirt5のデスクシニラゼとデマロニラゼの活性を決定するためのインビトロ酵素分析.
- 哺乳類におけるサクシニレートおよびマロニレートタンパク質を特定するための質量スペクトロメトリー.
- Sirt5ノックアウトマウスの分析で,タンパク質サクシニレーションに対するインビボ効果を評価した.
主要な成果:
- Sirt5は,タンパク質ライシンデシニラーゼとデマロニラーゼの有効な活性性を in vitro で実証しました.
- Sirt5のアシルポケットの特定の残留物 (Arg105,Tyr102) は,基板好みの鍵として特定されました.
- Sirt5欠乏したマウスでは,カルバモイルリン酸塩合成酵素1のサクシニレーションの増加が観察されました.
結論:
- Sirt5は,主要なデスクシニラゼおよびデマロニラゼとして機能し,特定の翻訳後の修正を逆転させます.
- タンパク質リジンサクシニレーションは,Sirt5によって in vivo 制御される可逆的な変化です.
- Sirt5は,デスクシニレーションを通じて代謝経路の調節に重要な役割を果たしています.
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