フルクトーゼ-1,6-ビスホスファートアルドラーゼ/フォスファタゼの二機能性の構造的基礎
Shinya Fushinobu1, Hiroshi Nishimasu, Daiki Hattori
1Department of Biotechnology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Nature
|October 11, 2011
まとめ
古代の果糖-1,6-ビスホスファート (FBP) アルドラーゼ/フォスファターゼ (FBPA/P) は,単一の活性部位を用いて2つの異なる反応を特異的に触媒化する. 構造分析は,この二重の酵素的機能を可能にする動的活性部位の変化を明らかにします.
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
- 構造生物学 構造生物学とは
背景:
- 酵素は,通常,特定の生化学反応を1つ触媒化する.
- 二機能酵素は,通常,明確な触媒ドメインまたは乱交的な活性部位を持っています.
- 古代の果糖-1,6-ビスホスファート (FBP) アルドラーゼ/フォスファターゼ (FBPA/P) は例外であり,単一のドメイン内の2つの異なる反応を触媒化する.
研究 の 目的:
- 考古 FBPA/P.の二重触媒作用の背後にある分子メカニズムを解明する.
- 単一の酵素活性部位が,化学的に異なる2つの反応をどのように実行できるかを理解する.
主な方法:
- アルドラーゼ形式のFBPA/Pの1.5-Å解像度構造を決定するためのX線結晶学.
- アルドラーゼと以前に決定された酵素のフォスファターゼ形態の構造的比較.
主要な成果:
- 結晶構造は,アルドーラゼ形式の二酸化水素アセトンリン酸 (DHAP) とシフ基を形成する重要なリジン残基を明らかにした.
- アルドラーゼとフォスファタゼの形態を比較すると,活性部位における重要な形状の変化が観察されました.
- FBPA/Pはアクティブサイトアーキテクチャをダイナミックに変更して,ダブル触媒機能に対応します.
結論:
- 考古学的なFBPA/Pは,活性部位の変形を通して,新しい二機能性のメカニズムを示しています.
- この発見は,一つの酵素活性部位が単一の生化学反応に責任を負うという従来の理解に異議を唱えます.
- この研究は,酵素触媒戦略の既知のレパートリーを拡張します.
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