Amicoumacin A induces cancer cell death by targeting the eukaryotic ribosome.

Autor: Prokhorova IV; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR7104, Université de Strasbourg, 67404, Illkirch, France., Akulich KA; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119234 Russia.; School of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, 119234 Russia., Makeeva DS; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119234 Russia.; School of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, 119234 Russia., Osterman IA; Department of Chemistry, Lomonosov Moscow State University, Moscow, 119234 Russia., Skvortsov DA; Department of Chemistry, Lomonosov Moscow State University, Moscow, 119234 Russia., Sergiev PV; Department of Chemistry, Lomonosov Moscow State University, Moscow, 119234 Russia., Dontsova OA; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119234 Russia.; Department of Chemistry, Lomonosov Moscow State University, Moscow, 119234 Russia., Yusupova G; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR7104, Université de Strasbourg, 67404, Illkirch, France., Yusupov MM; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR7104, Université de Strasbourg, 67404, Illkirch, France., Dmitriev SE; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119234 Russia.; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia.; Department of Biochemistry, Biological Faculty, Lomonosov Moscow State University, Moscow, 119234 Russia.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2016 Jun 14; Vol. 6, pp. 27720. Date of Electronic Publication: 2016 Jun 14.
DOI: 10.1038/srep27720
Abstrakt: Amicoumacin A is an antibiotic that was recently shown to target bacterial ribosomes. It affects translocation and provides an additional contact interface between the ribosomal RNA and mRNA. The binding site of amicoumacin A is formed by universally conserved nucleotides of rRNA. In this work, we showed that amicoumacin A inhibits translation in yeast and mammalian systems by affecting translation elongation. We determined the structure of the amicoumacin A complex with yeast ribosomes at a resolution of 3.1  Å. Toxicity measurement demonstrated that human cancer cell lines are more susceptible to the inhibition by this compound as compared to non-cancerous ones. This might be used as a starting point to develop amicoumacin A derivatives with clinical value.
Databáze: MEDLINE
Externí odkaz: