3LWO

Structure of H/ACA RNP bound to a substrate RNA containing 5BrU

Summary for 3LWO

• Entry DOI: 10.2210/pdb3lwo/pdb
• Related: 3LWP 3LWQ 3LWR 3LWV
• Descriptor: Pseudouridine synthase Cbf5, Ribosome biogenesis protein Nop10, 50S ribosomal protein L7Ae, ... (7 entities in total)
• Functional Keywords: h/aca pseudouridine synthase, isomerase, trna processing, ribonucleoprotein, ribosome biogenesis, rrna processing, ribosomal protein, rna-binding, isomerase-rna binding protein-rna complex, isomerase/rna binding protein/rna
• Biological source: Pyrococcus furiosus; More
• Total number of polymer chains: 5
• Total formula weight: 82304.32

Authors

Zhou, J.,Liang, B.,Lv, C.,Yang, W.,Li, H. (deposition date: 2010-02-24, release date: 2010-07-14, Last modification date: 2011-07-13)

Primary citation

Zhou, J.,Lv, C.,Liang, B.,Chen, M.,Yang, W.,Li, H.
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, 2010

PubMed 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.

PubMed: 20615421
DOI: 10.1016/j.jmb.2010.06.061

Experimental method

X-RAY DIFFRACTION (2.855 Å)