在thymidylate synthase中的动态同位素效应的温度依赖性. 一个理论研究研究
Natalia Kanaan1, Silvia Ferrer, Sergio Martí
1Departament de Química Física i Analítica, Universitat Jaume I, 12071 Castellón, Spain.
Journal of the American Chemical Society
|April 12, 2011
概括
基酸合成酶中的温度独立的动态同位素效应 (KIEs) 是通过量子道和合蛋白运动来解释的. 这些因素确保了跨温度的一致的转移机制.
科学领域:
- 生物化学 生物化学
- 计算化学计算化学
- 酶动力学 酶动力学
背景情况:
- 初级动态同位素效应 (KIEs) 的温度依赖是酶催化H转移反应的物理性质的关键指标.
- 结合实验数据和计算模拟的交互研究对于准确解释KIE温度依赖是至关重要的.
研究的目的:
- 为了研究胺基酸合成酶催化反应的速度限制步骤.
- 用计算方法和实验数据解释KIEs的温度依赖性.
主要方法:
- 混合量子力学/分子力学 (QM/MM) 模拟.
- 集成平均变异过渡状态理论与多维道 (EA-VTST/MT).
- 对于动态交叉系数的格罗特-海恩斯理论.
主要成果:
- 计算的KIEs表现出温度独立的行为,与实验结果一致.
- 转移涉及显著的量子道化 (的≤91%,的≤80%).
- 蛋白质运动,特别是涉及Arg166和Cys146,与反应坐标显著配对,影响H转移概率.
结论:
- 在thymidylate synthase中观察到的温度独立的KIEs归因于量子道化,过渡状态几何学和合蛋白质动态的联合效应.
- 促进酶的振动限制了通过配置空间的搜索,通过道或经典机制增强了H转移的概率.
- 与反应坐标相结合的热波动在研究的温度范围内保持一致,从而导致不变的KIEs.
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