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Amicoumacin A induces cancer cell death by targeting the eukaryotic ribosome

by Akulich, Kseniya A. , Prokhorova, Irina V. , Osterman, Ilya A. , Dontsova, Olga A. , Makeeva, Desislava S. , Skvortsov, Dmitry A. , Dmitriev, Sergey E. , Yusupova, Gulnara , Sergiev, Petr V. , Yusupov, Marat M.

in 49/109 / 631/154/556 / 631/337/574/1789 / 631/535/1266 / 631/92/613 / 692/308/153 / Cell death / Cell Death - drug effects / Cell Line, Tumor / Coumarins - chemistry / Coumarins - pharmacology / Coumarins - toxicity / Crystallography, X-Ray / Eukaryota - metabolism / HEK293 Cells / Humanities and Social Sciences / Humans / Life Sciences / Models, Molecular / multidisciplinary / Protein Biosynthesis - drug effects / Ribosomes - drug effects / Ribosomes - metabolism / RNA, Messenger - genetics / RNA, Messenger - metabolism / Saccharomyces cerevisiae - drug effects / Saccharomyces cerevisiae - metabolism / Science / Translocation / Yeasts

2016

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Amicoumacin A induces cancer cell death by targeting the eukaryotic ribosome

2016

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2016

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Journal Article

Amicoumacin A induces cancer cell death by targeting the eukaryotic ribosome

Akulich, Kseniya A.,

Prokhorova, Irina V.,

Osterman, Ilya A.,

Dontsova, Olga A.,

Makeeva, Desislava S.,

Skvortsov, Dmitry A.,

Dmitriev, Sergey E.,

Yusupova, Gulnara,

Sergiev, Petr V.,

Yusupov, Marat M.

2016

Overview

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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Nature Publishing Group UK,Nature Publishing Group

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