協調的な複数の陽子伝送のための動的同位体効果:炭酸アンヒドラゼIIのアクティブサイトモデルの直接ダイナミクス研究
Zorka Smedarchina1, Willem Siebrand, Antonio Fernández-Ramos
1Steacie Institute for Molecular Sciences, National Research Council of Canada, Ottawa, Ontario, Canada K1A 0R6. Zorka.Smedarchina@nrc.ca
Journal of the American Chemical Society
|January 8, 2003
まとめ
炭酸アンヒドラゼII 炭酸アンヒドラゼII 炭酸アンヒドラゼII 炭酸アンヒドラゼII 炭酸アンヒドラゼII 炭酸アンヒドラゼII 炭酸アンヒドラゼII
科学分野:
- バイオケミストリー バイオケミストリー
- コンピューティング・ケミストリー
- エンジム・キネティクス
背景:
- 炭酸アンヒドラゼIIは,体液から二酸化炭素を排出するのに不可欠です.
- 酵素の活性部位の構造は知られているが,水分子の配置は不明である.
- ウォーターブリッジ経由の陽子伝達は,速度を制限するステップです.
研究 の 目的:
- アクティブサイトモデルを使用して,炭酸アンヒドラゼIIの反応速度定数を計算します.
- トンネリングを含む陽子伝送のメカニズムを調査する.
- 計算結果を実験データと比較する.
主な方法:
- 亜鉛イオンとメチリミダゾールを含む58個の原子を用いたアクティブサイトモデリング.
- 構造と力場計算のための近似密度関数理論 (SCC-DFTB).
- 直動力学の計算は,近似インスタントン法と変数移行状態理論を用いて行われます.
主要な成果:
- 単一の移行状態は,協調した三重陽子の移転を示唆する.
- 量子計算は実験よりも高い率とKIEを示しています.
- 古典的な計算では,利率が低いが,KIEが著しく高い.
- トンネリングは,陽子転送の主要なメカニズムとして確認されています.
- 2つの水橋のモデルは,濃度が低いものの,陽子輸送には非常に効率的です.
結論:
- 炭酸アンヒドラゼIIにおけるプロトン伝達は,2つの水の橋を通るトンネルの経由で発生する.
- 2つの水橋のメカニズムは,酵素の高い触媒効率に不可欠です.
- 協調的な移転は,KIEがデウテリウム濃度に依存していることによって支持されています.
- このメカニズムは,段階的な転送を使用するより効率が低い同酵素と異なる.
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