The Pseudouridine Synthases Proceed through a Glycal Intermediate.
The Pseudouridine Synthases Proceed through a Glycal Intermediate.
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DOI：
10.1021/jacs.6b04491
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发表时间：
2016-06-29
影响因子：
15
通讯作者：
Mueller EG
中科院分区：
文献类型：
--
作者：
Veerareddygari GR;Singh SK;Mueller EG
假尿苷合酶将RNA中的尿苷（U）异构化为假尿苷（Ψ），它们所遵循的机制长期以来一直是人们感兴趣的问题。最近对一种已差向异构化为阿拉伯糖异构体的机制探针5 - 氟尿苷产物的阐释表明，Ψ合酶可能通过一个由C2′去质子化形成的烯糖中间体起作用。当底物U中的该位置被氘代时，观察到了一级动力学同位素效应，这无可争议地表明，所提出的去质子化发生在U到Ψ的异构化过程中，并确定了Ψ合酶所遵循的机制。
The pseudouridine synthases isomerize (U) in RNA to pseudouridine (Ψ), and the mechanism that they follow has long been a question of interest. The recent elucidation of a product of the mechanistic probe 5-fluorouridine that had been epimerized to the arabino isomer suggested that the Ψ synthases might operate through a glycal intermediate formed by deprotonation of C2′. When that position in substrate U is deuterated, a primary kinetic isotope effect is observed, which indisputably indicates that the proposed deprotonation occurs during the isomerization of U to Ψ and establishes the mechanism followed by the Ψ synthases.