水網は,タンパク質-リガンド結合におけるエンタルピー/エントロピーの補償に寄与する

Benjamin Breiten¹, Matthew R Lockett, Woody Sherman

¹Department of Chemistry and Chemical Biology, Harvard University , 12 Oxford Street, Cambridge, Massachusetts 02138, United States.

Journal of the American Chemical Society

|September 19, 2013

まとめ

タンパク質-リガンド結合におけるエンタルピー-エントロピーの補償は,ヒト炭酸アンヒドラゼとフッ素リガンドを用いて明確にされる. 水水水水水でした.

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
化学熱力学化学熱力学

背景:

タンパク質-リガンド結合メカニズムにおけるエンタルピー-エントロピー (H/S) 補償は議論されている.
リガンド結合仮説を検証するための予測モデルが不足している.

研究の目的:

よく特徴づけられたタンパク質-リガンド系におけるH/S補償を熱力学的に,そして構造的に定義する.
生物分子認識の際にH/S補償における溶媒分子の役割を調査する.

主な方法:

ヒト炭酸アンヒドラゼ (HCA) と一連の化ベンゾチアゾール硫黄胺リガンドを使用した.
リガンド結合の熱力学および構造分析を行った.
タンパク質の活性部位における水分子の性質を調査した.

主要な成果:

HCAに対するリガンド結合親和性は,多種多様なフッ素化にもかかわらず,ほとんど区別できなかった.
結合のエンタルピーとエントロピーの有意で補償的な変化が観察されました.
周囲の水分子の構造と熱力学的性質の違いは,H/S補償に寄与する.

結論:

タンパク質の活性部位にある水分子は,生物分子認識と結合熱力学にとって極めて重要です.
溶媒効果は,直接のタンパク質-リガンド接触相互作用と同じくらい重要です.
H/S補償とその決定因子を研究するためのモデルシステムを提供します.

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