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

Polikanov, Y. S.; Osterman, I. A.; Szal, T.; Tashlitsky, V. N.; Serebryakova, M. V.; Kusochek, P.; Bulkley, D.; Malanicheva, I. A.; Efimenko, T. A.; Efremenkova, O. V.; Konevega, A. L.; Shaw, k.J.; Bogdanov, A. A.; Rodnina, M. V.; Dontsova, O. A.; Mankin, A. S.; Steitz, T. A.; Sergiev, P. V.

doi:10.1016/j.molcel.2014.09.020

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

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Rodnina, M. V.
Department of Physical Biochemistry, MPI for biophysical chemistry, Max Planck Society;

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Citation

Polikanov, Y. S., Osterman, I. A., Szal, T., Tashlitsky, V. N., Serebryakova, M. V., Kusochek, P., et al. (2014). Amicoumacin a inhibits translation by stabilizing mRNA interaction with the ribosome. Molecular Cell, 56(4), 531-540. doi:10.1016/j.molcel.2014.09.020.

Cite as: https://hdl.handle.net/11858/00-001M-0000-0023-F410-A

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.