既存の形状均衡の調節は,アデニル酸キナーゼの活性性を調節する

Jörgen Ådén¹, Abhinav Verma, Alexander Schug

¹Department of Chemistry, Chemical Biological Center, Umeå University, SE-901 87 Umeå, Sweden.

Journal of the American Chemical Society

|September 12, 2012

まとめ

アデニラートキナーゼ (AK ((eco)) の構造的可塑性は,その酵素活性に鍵を握っています. その構成均衡を調節すると,周回率と基板結合の両方に影響し,進化的柔軟性を提供します.

科学分野:

バイオケミストリーバイオケミストリー
構造生物学構造生物学とは
酵素学酵素学とは

背景:

酵素触媒は,反応サイクルにおける構造的可塑性に依存しています.
Escherichia coli (AK) のアデニラートキナーゼは,開いた状態 (無活性) と閉じた状態 (活性) に存在します.
AK ((eco) の酵素のターンオーバーは,その活性コンフォームの寿命と関連しています.

研究の目的:

サブストラットがない状態でAK ((eco)) の構成均衡を調査する.
この均衡が酵素触媒にどのように影響するかを理解する.
変異とオスモライトがAK ((eco)) の形状と活動に及ぼす影響を調査する.

主な方法:

核磁共振 (NMR) スペクトロスコーピー. 核磁共振 (NMR) スペクトロスコーピー. 核磁共振 (NMR) スペクトロスコーピー.
分子力学 (MD) シミュレーション.
サイト指向型変異性およびオスモライト治療.

主要な成果:

水素結合の除去により,平衡がオープンな形状にシフトし,k (((cat)) が増加した.
TMAOの添加は,閉じた形状に均衡を移し,k (((cat) を減少させた.
マイケリス定数 (K(M)) はk(cat) の変化と相関しており,基質結合親和性が変化していることを示している.

結論:

既存の構成均衡は,酵素触媒に直接影響を及ぼします.
k (cat) とK (M) は相互依存しており,構成集団の影響を受けています.
AK ((eco) は,細胞の選択圧力に基づいて,その特異性定数に適応する柔軟性を示す.

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