Summary information and primary citation

PDB-id
3lwo; SNAP-derived features in text and JSON formats; DNAproDB
Class
isomerase-RNA binding protein-RNA
Method
X-ray (2.855 Å)
Summary
Structure of h-aca rnp bound to a substrate RNA containing 5bru
Reference
Zhou J, Lv C, Liang B, Chen M, Yang W, Li H (2010): "Glycosidic bond conformation preference plays a pivotal role in catalysis of RNA pseudouridylation: a combined simulation and structural study." J.Mol.Biol., 401, 690-695. doi: 10.1016/j.jmb.2010.06.061.
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-bromouridine-containing substrate bound to the ribonucleoprotein particle pseudouridine synthase and enzyme activity assay confirmed the anti nonreactive conformation and provided the molecular basis for its confinement. The observed preference for the syn pre-reactive state by the enzyme-bound uridine may help to distinguish among currently proposed mechanisms.

Cartoon-block schematics in six views (download the tarball)

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