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

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.

SUBMITTER: Prokhorova IV

PROVIDER: S-EPMC4906347 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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

Prokhorova Irina V IV Akulich Kseniya A KA Makeeva Desislava S DS Osterman Ilya A IA Skvortsov Dmitry A DA Sergiev Petr V PV Dontsova Olga A OA Yusupova Gulnara G Yusupov Marat M MM Dmitriev Sergey E SE

Scientific reports 20160614

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 res ...[more]

PMID: 27296282

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Amicoumacin a inhibits translation by stabilizing mRNA interaction with the ribosome.

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