Conformational Excitation and Nonequilibrium Transition Facilitate Enzymatic Reactions: Application to Pin1 Peptidyl-Prolyl Isomerase
Conformational Excitation and Nonequilibrium Transition Facilitate Enzymatic Reactions: Application to Pin1 Peptidyl-Prolyl Isomerase
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构象激发和非平衡转变促进酶促反应：在 Pin1 肽基脯氨酰异构酶中的应用
DOI：
10.1021/acs.jpclett.8b03607
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Saito Shinji
中科院分区：
文献类型：
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作者：
Mori Toshifumi;Saito Shinji
蛋白质的构象柔性是酶催化的基础。然而，蛋白质的构象重排和动力学如何有助于催化仍然存在很大争议。要揭示蛋白质在催化中的作用，就必须同时理解其静态和动态机制。为此，本文从这两个角度对Pin1催化的异构化反应进行了研究。静态视图表明，涉及Pin1的氢键重排与异构化的紧耦合的方式。与此形成鲜明对比的是，异构化动力学被发现是非常迅速的，蛋白质的缓慢构象重排，因此不能同时发生异构化，反应进行的非平衡方式。稳定过渡态所需的独特蛋白质构象是先验制备的，即，作为构象激发态。这一结果表明，酶促反应不是简单的从平衡态直接到过渡态的热活化过程，从而为Pauling的观点提供了新的视角。
Conformational flexibility of protein is essential for enzyme catalysis. Yet, how protein’s conformational rearrangements and dynamics contribute to catalysis remains highly controversial. To unravel protein’s role in catalysis, it is inevitable to understand the static and dynamic mechanisms simultaneously. To this end, here the Pin1-catalyzed isomerization reaction is studied from the two perspectives. The static view indicates that the hydrogen bonds involving Pin1 rearrange in a tightly coupled manner with isomerization. In sharp contrast, the isomerization dynamics are found to be very rapid; protein’s slow conformational rearrangements thus cannot occur simultaneously with isomerization, and the reaction proceeds in a nonequilibrium manner. The distinctive protein conformations necessary to stabilize the transition state are prepared a priori, i.e., as conformational excited states. The present result suggests that enzymatic reaction is not a simple thermal activation from equilibrium directly to the transition state, thus adding a novel perspective to Pauling’s view.