形状压缩和偏好的过渡状态稳定对里沙酸突变酶增速的贡献
Cristiano Ruch Werneck Guimarães1, Matthew P Repasky, Jayaraman Chandrasekhar
1Department of Chemistry, Yale University, 225 Prospect Street, New Haven, Connecticut 06520-8107, USA.
Journal of the American Chemical Society
|June 5, 2003
概括
化基因突变酶 (CM) 通过压缩其基质的近攻击形态 (NACs),而不是预先组织它来加速反应. 这种由酶催化的压缩是以力控制的,这解释了在酶催化中观察到的显著速度提升.
科学领域:
- 生物化学 生化学
- 酶动力学 酶动力学
- 计算化学是一种计算化学.
背景情况:
- 霍里斯马特突变酶 (CM) 催化了关键的克莱森重组.
- 了解酶催化速率增强是酶机制研究的关键.
研究的目的:
- 调查近攻击形态 (NACs) 在 chorismate 突变酶 (CM) 催化反应中的作用.
- 阐明CM提供的利率提升背后的机制.
主要方法:
- 联合量子力学/分子力学 (QM/MM) 模拟.
- 蒙特卡洛/自由能量扰动 (MC/FEP) 的计算.
- 在溶液和活性位点中分析基质构造偏好.
主要成果:
- 化物主要存在于NAC结构中的水 (82%) 和CM活性部位 (100%) 中.
- 酶预组织成NACs不会对激活自由能量做出贡献.
- 速率的增强主要是由于酶对NAC的形状性压缩,这是一个受热量控制的过程.
结论:
- CM的主要催化机制涉及接近攻击形状的体驱动的形状压缩.
- 优选的过渡状态稳定在CM催化中起着次要的作用.
- 计算方法准确地复制了对酶活性的实验观测.
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