エシェリキヤ大腸二酸化水素葉酸還元酵素による触媒に対する溶媒の効果
E Joel Loveridge1, Lai-Hock Tey, Rudolf K Allemann
1School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff CF10 3AT, UK.
Journal of the American Chemical Society
|January 6, 2010
まとめ
反応媒体の粘度ではなく,介電定数によって,二酸化葉酸還元酵素 (DHFR) によって触媒化された水素移転の速度に影響されます. 溶媒の変化は,運動同位体効果や温度依存性に影響しませんでした.
科学分野:
- バイオケミストリー バイオケミストリー
- 酵素の動力学について
- タンパク質のダイナミクス
背景:
- ディヒドロフォラート還元酵素 (DHFR) は,環境結合水素トンネリングを通じて水素移転を触媒化する.
- タンパク質の動きは,基板/共因子結合を制御し,活性化バリアの幅を調節し,反応速度に影響を与えると考えられています.
- 反応媒体の組成の変化は,タンパク質の動きを乱す可能性があります.
研究 の 目的:
- 反応媒体の組成がDHFR触媒化ヒドリド移転の動力学に及ぼす影響を調査する.
- 介電常数や介質の粘度が酵素触媒に影響するかどうかを判断する.
- 溶媒の特性と水素移転のメカニズムとの関係を調査する.
主な方法:
- Escherichia coli DHFRの運動パラメータは,様々なコソルベンツやコソルトの存在下で測定されました.
- 動的同位体効果とその温度依存性を分析した.
- Thermotoga maritima.よりDHFRに関する以前の研究と結果の比較.
主要な成果:
- 反応媒体の介電常数は反応速度に大きな影響を及ぼしたが,粘度には影響はなかった.
- 主要な運動同位体効果も,温度依存も,大量溶媒の特性によって変化しませんでした.
- E. coli DHFRの運動同位体効果の温度依存に対する溶媒の効果は,既存のモデルに課題を提示した.
結論:
- DHFRによる酵素触媒は,周囲の介質の介電特性に対して敏感である.
- 研究結果は,長距離の動きが唯一の決定因子ではないかもしれないが,短距離の振動や形状的サブステートがDHFR触媒に役割を果たす可能性があることを示唆している.
- DHFR触媒化ヒドリド移転に対する溶媒効果のメカニズムを完全に解明するには,さらなる調査が必要である.
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