酵素の進化における特異性と乱雑性のバランス:アルカリ性ファスファタゼ超家族における多次元の活動移行
Bert van Loo1, Christopher D Bayer1, Gerhard Fischer1
1Department of Biochemistry , University of Cambridge , Cambridge CB2 1GA , United Kingdom.
Journal of the American Chemical Society
|December 1, 2018
まとめ
多重反応を触媒化する酵素の能力は 機能的進化を容易にする. この研究は,アルカリ性ファスファタゼ超家族酵素が既存の機能を失うことなく新しい機能を進化させ,進化の経路の洞察を提供することを明らかにしています.
科学分野:
- 生物化学
- 進化生物学
- 構造生物学
背景:
- 高い触媒能力と乱交性を持つ酵素は機能的進化に不可欠であり,機能の喪失なしに適応を可能にします.
- アルカリリンフォスファタゼ (AP) スーパーファミリーは,その多様なメンバーと触媒能力により,酵素の進化を研究するためのモデルを提供します.
研究 の 目的:
- APスーパーファミリー内の乱交酵素の特異性と反応性の進化を体系的に追跡する.
- 構造,配列,基板特異性の比較分析を用いて,アリル硫酸塩 (ASs) とフォスフォン酸エステル水素酸塩 (PMHs) の間の移行領域を調査する.
主な方法:
- タンパク質の配列を系統的に分析して 進化的関係をマッピングする
- 酵素活動と速度加速を特徴付けるための運動分析.
- 酵素構造と基板の相互作用を理解するための結晶学.
主要な成果:
- 特徴づけられたすべての酵素は,4つの異なるフォスフォエステラーゼ活性を示し,主反応と乱交反応の両方の速度が著しく加速した.
- 既知のPMHに非常に類似する新種のASが特定され,以前は認識されなかった機能的差異を示した.
- 移行中の酵素の分析は,機能的進化と活動間のトレードオフのモデルを明らかにしました.
結論:
- 触媒的乱交はAP超家族で広く存在し 機能的な進化の跳躍台として機能しています
- 新しいASにおける不変基質特異性によって示されるトレードオフフリー分子エクサプテーションは,初期機能の喪失なしに進化を可能にします.
- この進化的メカニズムは,新しい酵素機能の出現中に適応的衝突を回避するための解決策を提供します.
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