Amicoumacin A induces cancer cell death by targeting the eukaryotic ribosome.
Fiche publication
Date publication
juin 2016
Journal
Scientific reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr YUSUPOV Marat, Dr YUSUPOVA Gulnara
Tous les auteurs :
Prokhorova IV, Akulich KA, Makeeva DS, Osterman IA, Skvortsov DA, Sergiev PV, Dontsova OA, Yusupova G, Yusupov MM, Dmitriev SE
Lien Pubmed
Résumé
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.
Mots clés
Cell Death, drug effects, Cell Line, Tumor, Coumarins, chemistry, Crystallography, X-Ray, Eukaryota, metabolism, HEK293 Cells, Humans, Models, Molecular, Protein Biosynthesis, drug effects, RNA, Messenger, genetics, Ribosomes, drug effects, Saccharomyces cerevisiae, drug effects
Référence
Sci Rep. 2016 06 14;6:27720