selective pharmacological targeting of a dead box rna helicaserna解旋酶选择性药物针对死亡的盒子.pdfVIP

Selective Pharmacological Targeting of a DEAD Box RNA Helicase 1 2 2 1 1 3 Lisa Lindqvist , Monika Oberer , Mikhail Reibarkh , Regina Cencic , Marie-Eve Bordeleau , Emily Vogt , 2 4 3 5 2 Assen Marintchev , Junichi Tanaka , Francois Fagotto , Michael Altmann , Gerhard Wagner , Jerry Pelletier1,6* 1 Department of Biochemistry, McGill University, Montreal, Quebec, Canada, 2 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, United States of America, 3 Department of Biology, McGill University, Montreal, Quebec, Canada, 4 Department of Chemistry, Biology, and Marine ¨ ¨ Sciences, University of the Ryukyus, Nishihara, Okinawa, Japan, 5 Institut fur Biochemie und Molekulare Medizin, Universitat Bern, Bern, Switzerland, 6 McGill Cancer Center, McGill University, Montreal, Quebec, Canada Abstract 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 pr