Glycosidic bond conformation preference plays a pivotal role in catalysis of RNA pseudouridylation: a combined simulation and structural study.

ABSTRACT: The most abundant chemical modification on RNA is isomerization of uridine (or pseudouridylation) catalyzed by pseudouridine synthases. The catalytic mechanism of this essential process remains largely speculative, partly due to lack of knowledge of the pre-reactive state that is important to the identification of reactive chemical moieties. In the present study, we showed, using orthogonal space random-walk free-energy simulation, that the pre-reactive states of uridine and its reactive derivative 5-fluorouridine, bound to a ribonucleoprotein particle pseudouridine synthase, strongly prefer the syn glycosidic bond conformation, while that of the nonreactive 5-bromouridine-containing substrate is largely populated in the anti conformation state. A high-resolution crystal structure of the 5

SUBMITTER: Zhou J 

PROVIDER: S-EPMC2938745 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature