Amicoumacin A induces cancer cell death by targeting the eukaryotic ribosome

  • Sci Rep. 2016 Jun 14:6:27720. doi: 10.1038/srep27720.
Irina V Prokhorova  1 ,  Kseniya A Akulich  2  3 ,  Desislava S Makeeva  2  3 ,  Ilya A Osterman  4 ,  Dmitry A Skvortsov  4 ,  Petr V Sergiev  4 ,  Olga A Dontsova  2  4 ,  Gulnara Yusupova  1 ,  Marat M Yusupov  1 ,  Sergey E Dmitriev  2  5  6
Affiliations
  • 1. Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR7104, Université de Strasbourg, 67404, Illkirch, France.
  • 2. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119234 Russia.
  • 3. School of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, 119234 Russia.
  • 4. Department of Chemistry, Lomonosov Moscow State University, Moscow, 119234 Russia.
  • 5. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia.
  • 6. Department of Biochemistry, Biological Faculty, Lomonosov Moscow State University, Moscow, 119234 Russia.
PMID: 27296282 DOI: 10.1038/srep27720
Abstract

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.

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