Amicoumacin A induces cancer cell death by targeting the eukaryotic ribosome.
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.
Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR7104, Université de Strasbourg, 67404, Illkirch, France.
Irina V
IV
Prokhorova
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.
Kseniya A
KA
Akulich
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.
Desislava S
DS
Makeeva
Department of Chemistry, Lomonosov Moscow State University, Moscow, 119234 Russia.
Ilya A
IA
Osterman
Department of Chemistry, Lomonosov Moscow State University, Moscow, 119234 Russia.
Dmitry A
DA
Skvortsov
Department of Chemistry, Lomonosov Moscow State University, Moscow, 119234 Russia.
Petr V
PV
Sergiev
Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119234 Russia.|Department of Chemistry, Lomonosov Moscow State University, Moscow, 119234 Russia.
Olga A
OA
Dontsova
Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR7104, Université de Strasbourg, 67404, Illkirch, France.
Gulnara
G
Yusupova
Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR7104, Université de Strasbourg, 67404, Illkirch, France.
Marat M
MM
Yusupov
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.
Sergey E
SE
Dmitriev
D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D018360:Crystallography, X-Ray; D056890:Eukaryota / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008958:Models, Molecular; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000187:drug effects / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism
D003374:Coumarins; D012333:RNA, Messenger; C031379:amicoumacin A