ArticleProceedings of the National Academy of Sciences of the United States of America2014
Negamycin induces translational stalling and miscoding by binding to the small subunit head domain of the Escherichia coli ribosome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 47 citations in OpenAlex.
- Negamycin: Nature's Forgotten Antibiotic.ACS infectious diseases · 2026Review
- Saskemycin, a potent and selective antimycobacterial agent targeting a unique site on the ribosome.Research square · 2025Article
- Article
- Impacts of ribosomal RNA sequence variation on gene expression and phenotype.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- Fighting Antimicrobial Resistance: Innovative Drugs in Antibacterial Research.Angewandte Chemie (International ed. in English) · 2025Review
- A Broad Spectrum Lasso Peptide Antibiotic Targeting the Bacterial Ribosome.Research square · 2024Article
- The Development of a Sulfamate-Tethered Aza-Michael Cyclization Allows for the Preparation of (-)-NegamycinThe Journal of organic chemistry · 2024Article
- Streptothricin F is a bactericidal antibiotic effective against highly drug-resistant gram-negative bacteria that interacts with the 30S subunit of the 70S ribosome.PLoS biology · 2023Article
- 2-Guanidino-quinazoline promotes the readthrough of nonsense mutations underlying human genetic diseases.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Ring Opening of Aziridines by Pendant Silanols Allows for Preparations of (±)-Clavaminol H, (±)-Des-Acetyl-Clavaminol H, (±)-Dihydrosphingosine, and (±)-Organic letters · 2022Article
- Repurposing tRNAs for nonsense suppression.Nature communications · 2021Article
- The Antibiotic Negamycin Crosses the Bacterial Cytoplasmic Membrane by Multiple Routes.Antimicrobial agents and chemotherapy · 2021Article
- A Quick Guide to Small-Molecule Inhibitors of Eukaryotic Protein Synthesis.Biochemistry. Biokhimiia · 2020Review
- Genome-wide effects of the antimicrobial peptide apidaecin on translation termination in bacteria.eLife · 2020Article
- Discovery of a novel small molecular peptide that disrupts helix 34 of bacterial ribosomal RNA.RSC advances · 2019Article
- A Much-Needed Boost for the Dwindling Antibiotic Pipeline.Molecular cell · 2018Article
- Chemotherapeutics overcoming nonsense mutation-associated genetic diseases: medicinal chemistry of negamycin.The Journal of antibiotics · 2018Review
- The Mechanisms of Action of Ribosome-Targeting Peptide Antibiotics.Frontiers in molecular biosciences · 2018Review
- Bacterial Protein Synthesis as a Target for Antibiotic Inhibition.Cold Spring Harbor perspectives in medicine · 2016Review
- Resistance mutations generate divergent antibiotic susceptibility profiles against translation inhibitors.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
Negamycin is a natural product with broad-spectrum antibacterial activity and efficacy in animal models of infection. Although its precise mechanism of action has yet to be delineated, negamycin inhibits cellular protein synthesis and causes cell death. Here, we show that single point mutations within 16S rRNA that confer resistance to negamycin are in close proximity of the tetracycline binding site within helix 34 of the small subunit head domain. As expected from its direct interaction with this region of the ribosome, negamycin was shown to displace tetracycline. However, in contrast to tetracycline-class antibiotics, which serve to prevent cognate tRNA from entering the translating ribosome, single-molecule fluorescence resonance energy transfer investigations revealed that negamycin specifically stabilizes near-cognate ternary complexes within the A site during the normally transient initial selection process to promote miscoding. The crystal structure of the 70S ribosome in complex with negamycin, determined at 3.1 Å resolution, sheds light on this finding by showing that negamycin occupies a site that partially overlaps that of tetracycline-class antibiotics. Collectively, these data suggest that the small subunit head domain contributes to the decoding mechanism and that small-molecule binding to this domain may either prevent or promote tRNA entry by altering the initial selection mechanism after codon recognition and before GTPase activation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.