ArticleProceedings of the National Academy of Sciences of the United States of America2016
Structures of the orthosomycin antibiotics avilamycin and evernimicin in complex with the bacterial 70S ribosome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 61 citations in OpenAlex.
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- Oxydifficidin, a potenteLife · 2025Article
- An NADH/NADApplied and environmental microbiology · 2024Article
- Characterization of Dichloroisoeverninic Acid Biosynthesis and Chemoenzymatic Synthesis of New Orthosomycins.ACS chemical biology · 2024Article
- Hibernating ribosomes as drug targets?Frontiers in microbiology · 2024Review
- Geometric alignment of aminoacyl-tRNA relative to catalytic centers of the ribosome underpins accurate mRNA decoding.Nature communications · 2023Article
- Structural conservation of antibiotic interaction with ribosomes.Nature structural & molecular biology · 2023Article
- Ribosome-targeting antibiotics and resistanceRSC medicinal chemistry · 2023Review
- Sarecycline inhibits protein translation in Cutibacterium acnes 70S ribosome using a two-site mechanism.Nucleic acids research · 2023Article
- Context-based sensing of orthosomycin antibiotics by the translating ribosome.Nature chemical biology · 2022Article
- Optimal Regimens and Clinical Breakpoint of Avilamycin AgainstFrontiers in pharmacology · 2022Article
- Structural basis of l-tryptophan-dependent inhibition of release factor 2 by the TnaC arrest peptide.Nucleic acids research · 2021Article
- Article
- Microbial Oligosaccharides with Biomedical Applications.Marine drugs · 2021Review
- Structure of the mature kinetoplastids mitoribosome and insights into its large subunit biogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Bifunctional Nitrone-Conjugated Secondary Metabolite Targeting the Ribosome.Journal of the American Chemical Society · 2020Article
- Structural analysis of 70S ribosomes by cross-linking/mass spectrometry reveals conformational plasticity.Scientific reports · 2020Article
- Elongation Factor Tu Switch I Element is a Gate for Aminoacyl-tRNA Selection.Journal of molecular biology · 2020Article
- Antibiotics targeting bacterial ribosomal subunit biogenesis.The Journal of antimicrobial chemotherapy · 2020Review
- Elongation factor-Tu can repetitively engage aminoacyl-tRNA within the ribosome during the proofreading stage of tRNA selection.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The ribosome is one of the major targets for therapeutic antibiotics; however, the rise in multidrug resistance is a growing threat to the utility of our current arsenal. The orthosomycin antibiotics evernimicin (EVN) and avilamycin (AVI) target the ribosome and do not display cross-resistance with any other classes of antibiotics, suggesting that they bind to a unique site on the ribosome and may therefore represent an avenue for development of new antimicrobial agents. Here we present cryo-EM structures of EVN and AVI in complex with the Escherichia coli ribosome at 3.6- to 3.9-Å resolution. The structures reveal that EVN and AVI bind to a single site on the large subunit that is distinct from other known antibiotic binding sites on the ribosome. Both antibiotics adopt an extended conformation spanning the minor grooves of helices 89 and 91 of the 23S rRNA and interacting with arginine residues of ribosomal protein L16. This binding site overlaps with the elbow region of A-site bound tRNA. Consistent with this finding, single-molecule FRET (smFRET) experiments show that both antibiotics interfere with late steps in the accommodation process, wherein aminoacyl-tRNA enters the peptidyltransferase center of the large ribosomal subunit. These data provide a structural and mechanistic rationale for how these antibiotics inhibit the elongation phase of protein synthesis.
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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.