对速率常数和运动同位素效应的理论分析,对应于乳酸脱酶中的不同反应物谷
Silvia Ferrer1, Iñaki Tuñón, Sergio Martí
1Departament de Química Física, Universitat de València, València, Spain.
Journal of the American Chemical Society
|December 21, 2006
概括
乳酸脱酶的计算分析揭示了酶活性位点动态如何影响反应速率. 不同的反应物复合物导致不同的催化速度,由动态同位素效应验证.
科学领域:
- 生物化学 生物化学
- 计算化学的计算化学
- 酶学 是一种酶学.
背景情况:
- 酶反应可以表现出可变速率常数,这是由于与化学步骤相结合的结构变化造成的.
- 单分子实验揭示了与不同反应物谷相关的速率常数分散.
研究的目的:
- 以计算方式研究由乳酸脱酶催化的pyruvate到乳酸转化.
- 了解活性部位动态和反应物复杂变异如何影响反应速率和机制.
主要方法:
- 自由能量扰动技术以估计沿着内在反应坐标的速率常数.
- 集成平均变异过渡状态理论与多维道为道效应.
- 分析活性部位的残留物排放,基质相互作用和水分子存在.
主要成果:
- 乳酸脱酶活性部位通过柔性循环的关闭形成了独特的反应物复合物.
- 这些复合物在关键的残留安排 (例如,Arg109),基质相互作用和水合等方面表现出差异.
- 化学步骤以不同的速度进行,取决于特定的反应物复合物,受异步和能量障碍的影响.
- 计算的初级动态同位素效应与实验数据保持一致.
结论:
- 酶活性部位的灵活性和由此产生的构造状态是催化效率的关键决定因素.
- 使用的计算方法通过其与实验性动态同位素效应的一致性得到验证.
- 了解这些动态,可以深入了解酶催化和反应速率调节.
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