Transition-state theory has provided the theoretical framework to explain the enormous rate accelerations of chemical reactions by enzymes. Given that proteins display large ensembles of conformations, unique transition states would pose a huge entropic bottleneck for enzyme catalysis. To shed light on this question, we studied the nature of the enzymatic transition state for the phosphoryl-transfer step in adenylate kinase by quantum-mechanics/molecular-mechanics calculations. We find a structurally wide set of energetically equivalent configurations that lie along the reaction coordinate and hence a broad transition-state ensemble (TSE). A conformationally delocalized ensemble, including asymmetric transition states, is rooted in the macroscopic nature of the enzyme. The computational results are buttressed by enzyme kinetics experiments that confirm the decrease of the entropy of activation predicted from such wide TSE. Transition-state ensembles as a key for efficient enzyme catalysis further boosts a unifying concept for protein folding and conformational transitions underlying protein function.

中文翻译：

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宽过渡态系综作为酶催化的关键组成部分

过渡态理论提供了解释酶化学反应速率巨大加速的理论框架。鉴于蛋白质显示出大量的构象，独特的过渡态将为酶催化造成巨大的熵瓶颈。为了阐明这个问题，我们通过量子力学/分子力学计算研究了腺苷酸激酶中磷酰基转移步骤的酶过渡态的性质。我们发现了一组结构广泛的能量等效构型，它们沿着反应坐标，因此是一个广泛的过渡态系综（TSE）。构象离域整体，包括不对称过渡态，植根于酶的宏观性质。计算结果得到了酶动力学实验的支持，这些实验证实了从如此宽的 TSE 预测的激活熵的减少。过渡态整体作为有效酶催化的关键，进一步促进了蛋白质功能基础上蛋白质折叠和构象转变的统一概念。