Amicoumacin a Inhibits Translation by Stabilizing MRNA Interaction with the Ribosome

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2014 Oct 14

PMID 25306919

Citations 50

Authors

Yury S Polikanov

Ilya A Osterman

Teresa Szal

Vadim N Tashlitsky

Marina V Serebryakova

Pavel Kusochek

David Bulkley

Irina A Malanicheva

Tatyana A Efimenko

Olga V Efremenkova

Andrey L Konevega

Karen J Shaw

Alexey A Bogdanov

Marina V Rodnina

Olga A Dontsova

Alexander S Mankin

Thomas A Steitz

Petr V Sergiev

Affiliations

Soon will be listed here.

Abstract

We demonstrate that the antibiotic amicoumacin A (AMI) is a potent inhibitor of protein synthesis. Resistance mutations in helix 24 of the 16S rRNA mapped the AMI binding site to the small ribosomal subunit. The crystal structure of bacterial ribosome in complex with AMI solved at 2.4 Å resolution revealed that the antibiotic makes contacts with universally conserved nucleotides of 16S rRNA in the E site and the mRNA backbone. Simultaneous interactions of AMI with 16S rRNA and mRNA and the in vivo experimental evidence suggest that it may inhibit the progression of the ribosome along mRNA. Consistent with this proposal, binding of AMI interferes with translocation in vitro. The inhibitory action of AMI can be partly compensated by mutations in the translation elongation factor G.

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