非正規の近隣ヘムリガンドは,グロービン折れで効率的な過酸化剤を提供する
Moritz Pott1, Takahiro Hayashi1, Takahiro Mori1
1Laboratory of Organic Chemistry, ETH Zurich , Zurich 8093, Switzerland.
Journal of the American Chemical Society
|January 9, 2018
まとめ
研究者は改造されたヘム結合体でミオグロビンの変種を設計し,その酸化還元力を高め,強力な過酸化酵素を作り出した. この合成されたタンパク質は 自然の過酸化剤に匹敵する活性を示している.
科学分野:
- 生物化学
- タンパク質工学
- 酵素触媒
背景:
- 遺伝的にコードされた金属の調整環境は,改良されたまたは新しい機能を持つ金属酵素の開発を可能にします.
- 酸素結合タンパク質であるミオグルビン (Mb) は,生物触媒を生成するために設計できます.
研究 の 目的:
- 非正規のNδ-メチルヒスティジン (NMH) をミオグロビンに近接性ヘムリガンドとして組み込む影響を調査する.
- 効率的な過酸化生物触媒を 調節可能なタンパク質構造で設計する
主な方法:
- サイト・ダイレクト・ミュータジェネシスにより,Nδ-メチルヒスティジン (NMH) をミオグロビンに導入する.
- 改造されたミオグロビン変種 (Mb NMH) の構造的特徴
- ペロキシダースの活性を最適化するための実験室での進化と合理的な改変.
主要な成果:
- NMHを導入すると,ミオグロビンのヘム・レドックス・ポテンシャルとプロミスキュアス・ペロキシダース活性が大幅に増加した.
- 構造分析により,Mb NMHの近隣のポケットにおける水素結合の相互作用が変化したことが明らかになった.
- エンジニアリングされたMb NMHの変種は,天然の過酸化剤に匹敵する過酸化剤の活性を示した.
結論:
- 非正規のアミノ酸の組み込みは,タンパク質の機能的レパートリーを拡大するための有効な戦略です.
- 合成されたミオグロビンは 効率的な人工ペロキシダース生物触媒として機能します
- この研究は,特化した触媒特性を持つ新しい金属酵素を開発するためのプラットフォームを提供します.
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