Lindqvist, Lisa; Oberer, Monika; Reibarkh, Mikhail; Cencic, Regina; Bordeleau, Marie-Eve; Vogt, Emily; Marintchev, Assen; Tanaka, Junichi; Fagotto, Francois; Altmann, Michael; Wagner, Gerhard; Pelletier, Jerry (2008). Selective pharmacological targeting of a DEAD box RNA helicase. PLoS ONE, 3(2), e1583. Lawrence, Kans.: Public Library of Science 10.1371/journal.pone.0001583
Full text not available from this repository.RNA helicases represent a large family of proteins implicated in many biological processes including ribosome biogenesis, splicing, translation and mRNA degradation. However, these proteins have little substrate specificity, making inhibition of selected helicases a challenging problem. The prototypical DEAD box RNA helicase, eIF4A, works in conjunction with other translation factors to prepare mRNA templates for ribosome recruitment during translation initiation. Herein, we provide insight into the selectivity of a small molecule inhibitor of eIF4A, hippuristanol. This coral-derived natural product binds to amino acids adjacent to, and overlapping with, two conserved motifs present in the carboxy-terminal domain of eIF4A. Mutagenesis of amino acids within this region allowed us to alter the hippuristanol-sensitivity of eIF4A and undertake structure/function studies. Our results provide an understanding into how selective targeting of RNA helicases for pharmacological intervention can be achieved.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine |
UniBE Contributor: |
Altmann, Michael |
ISSN: |
1932-6203 |
ISBN: |
18270573 |
Publisher: |
Public Library of Science |
Language: |
English |
Submitter: |
Factscience Import |
Date Deposited: |
04 Oct 2013 15:05 |
Last Modified: |
05 Dec 2022 14:20 |
Publisher DOI: |
10.1371/journal.pone.0001583 |
PubMed ID: |
18270573 |
Web of Science ID: |
000260535900019 |
URI: |
https://boris.unibe.ch/id/eprint/28313 (FactScience: 119820) |
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