2014
DOI: 10.1016/j.molcel.2014.09.020
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Amicoumacin A Inhibits Translation by Stabilizing mRNA Interaction with the Ribosome

Abstract: SUMMARY We demonstrate that the antibiotic amicoumacin A (AMI) whose cellular target was unknown, 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… Show more

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Cited by 78 publications
(123 citation statements)
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“…1b). The present cryo-EM map visualizes for the first time modifications in rRNA, which were not observable in any of the high-resolution X-ray structures of the bacterial ribosome at 2.4-2.8 Å resolution 5,9 , and were only seen in high-resolution X-ray structures of the Haloarcula marismortui 50S subunit at 2.2-2.4 Å resolution 10 (Extended Data Fig. 4).…”
mentioning
confidence: 74%
“…1b). The present cryo-EM map visualizes for the first time modifications in rRNA, which were not observable in any of the high-resolution X-ray structures of the bacterial ribosome at 2.4-2.8 Å resolution 5,9 , and were only seen in high-resolution X-ray structures of the Haloarcula marismortui 50S subunit at 2.2-2.4 Å resolution 10 (Extended Data Fig. 4).…”
mentioning
confidence: 74%
“…The mode of action of amicoumacin A has been associated with inhibition of protein synthesis by suppressing the progression of the ribosome along the mRNA (Polikanov et al, 2014). Taken collectively, these results suggest that the mixture of antimicrobial compounds contained in crude B. licheniformis BFP011 supernatant may prove useful to prevent infections with food-borne pathogens.…”
Section: Scanning Electron Microscopymentioning
confidence: 89%
“…This work resulted in identification of the mechanism of action for antibiotic amicoumacin A [17]. Antibacterial activity of this antibiotic was described previously [6], however, its mechanism of action was revealed only in our study [17].…”
mentioning
confidence: 57%
“…This reporter construct was previously successfully applied for the screening of soil microorganisms culture broths provided by Gauze Institute of new antibiotics search [12]. This work resulted in identification of the mechanism of action for antibiotic amicoumacin A [17]. Antibacterial activity of this antibiotic was described previously [6], however, its mechanism of action was revealed only in our study [17].…”
mentioning
confidence: 74%
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