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The Pseudouridine Synthases Proceed through a Glycal Intermediate.

ABSTRACT: The pseudouridine synthases isomerize (U) in RNA to pseudouridine (?), 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 ? 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 ? and establishes the mechanism followed by the ? synthases.

SUBMITTER: Veerareddygari GR

PROVIDER: S-EPMC4929527 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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The Pseudouridine Synthases Proceed through a Glycal Intermediate.

Veerareddygari Govardhan Reddy GR Singh Sanjay K SK Mueller Eugene G EG

Journal of the American Chemical Society 20160617 25

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 t ...[more]

PMID: 27292228

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