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dc.contributor.authorLindqvist, Lisa
dc.contributor.authorOberer, Monika
dc.contributor.authorReibarkh, Mikhail
dc.contributor.authorCencic, Regina
dc.contributor.authorBordeleau, Marie-Eve
dc.contributor.authorVogt, Emily
dc.contributor.authorMarintchev, Assen
dc.contributor.authorTanaka, Junichi
dc.contributor.authorFagotto, Francois
dc.contributor.authorAltmann, Michael
dc.contributor.authorPelletier, Jerry
dc.contributor.authorWagner, Gerhard
dc.date.accessioned2010-12-22T21:34:34Z
dc.date.issued2008
dc.identifier.citationLindqvist, Lisa, Monika Oberer, Mikhail Reibarkh, Regina Cencic, Marie-Eve Bordeleau, Emily Vogt, Assen Marintchev, et al. 2008. Selective pharmacological targeting of a DEAD box RNA helicase. PLoS ONE 3(2): e1583.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4633726
dc.description.abstractRNA 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.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0001583en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2216682/pdf/en_US
dash.licenseLAA
dc.subjectchemical biologyen_US
dc.subjectbiochemistryen_US
dc.subjectdrug discoveryen_US
dc.subjecttranscription and translationen_US
dc.titleSelective Pharmacological Targeting of a DEAD Box RNA Helicaseen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorWagner, Gerhard
dc.date.available2010-12-22T21:34:34Z
dash.affiliation.otherHMS^Biological Chemistry and Molecular Pharmacologyen_US
dc.identifier.doi10.1371/journal.pone.0001583*
dash.authorsorderedfalse
dash.contributor.affiliatedWagner, Gerhard


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