ArticleProceedings of the National Academy of Sciences of the United States of America2008
Structural basis for cross-resistance to ribosomal PTC antibiotics.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. 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, 55 citations in OpenAlex.
- Effects of florfenicol on linezolid resistance in Enterococcus faecium from waterfowl farms.Poultry science · 2026Article
- How Medically Important Antimicrobials Bind to the 30S Ribosomal Subunit in a Bacterial Pathogen.Biochemistry · 2026Article
- Diversity in Adaptive Evolution of Methicillin-ResistantInfection and drug resistance · 2025Article
- Mechanisms of Linezolid Resistance in Mycobacteria.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Mapping the in vivo fitness landscape of a tethered ribosome.Science advances · 2023Article
- Insights into translocation mechanism and ribosome evolution from cryo-EM structures of translocation intermediates of Giardia intestinalis.Nucleic acids research · 2023Article
- Rare ribosomal RNA sequences from archaea stabilize the bacterial ribosome.Nucleic acids research · 2023Article
- Determination of In Vitro Antimicrobial Susceptibility for Lefamulin (Pleuromutilin) forAntibiotics (Basel, Switzerland) · 2021Article
- Characterization of compound A, a novel lincomycin derivative active against methicillin-resistant Staphylococcus aureus.The Journal of antibiotics · 2021Article
- Tiamulin-Resistant Mutants of the Thermophilic BacteriumAntibiotics (Basel, Switzerland) · 2020Article
- Expanding the Scope of Protein Synthesis Using Modified Ribosomes.Journal of the American Chemical Society · 2019Article
- The development of peptide ligands that target helix 69 rRNA of bacterial ribosomes.Bioorganic & medicinal chemistry · 2016Article
- Ribosomal Antibiotics: Contemporary Challenges.Antibiotics (Basel, Switzerland) · 2016Review
- Identification of the methyltransferase targeting C2499 in Deinococcus radiodurans 23S ribosomal RNA.Extremophiles : life under extreme conditions · 2016Article
- Structural insights into species-specific features of the ribosome from the pathogen Staphylococcus aureus.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Complex long-distance effects of mutations that confer linezolid resistance in the large ribosomal subunit.Nucleic acids research · 2015Article
- Macrolide-peptide conjugates as probes of the path of travel of the nascent peptides through the ribosome.ACS chemical biology · 2014Article
- Article
- GPU/CPU Algorithm for Generalized Born/Solvent-Accessible Surface Area Implicit Solvent Calculations.Journal of chemical theory and computation · 2012Article
- The chemistry of peptidyltransferase center-targeted antibiotics: enzymatic resistance and approaches to countering resistance.ACS chemical biology · 2012Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Clinically relevant antibiotics that target the ribosomal peptidyl transferase center (PTC), a highly conserved ribosomal region, exert their inhibitory action by exploiting the flexibility of PTC nucleotides, which trigger modulations of the shape of the antibiotic binding pocket. Resistance to these antibiotics was observed clinically and in vitro. Based on the crystal structures of the large ribosomal subunit from eubacterium suitable to represent pathogens in complex with these antibiotics, it was found that all nucleotides mediating resistance to PTC antibiotics cluster on one side of the PTC. Over half of the nucleotides affecting resistance reside in regions of lower sequence conservation, and are too distal to make Van der Waals interactions with the bound drugs. Alterations of the identity of these nucleotides may not lethally affect ribosome function, but can hamper antibiotic binding through changes in the conformation and flexibility of specific PTC nucleotides. Comparative analysis revealed properties likely to lead to cross-resistance and enabled their parameterization. As the same nucleotides are frequently involved in resistance to more than a single family of antibiotics, the common pattern explains medically observed cross-resistance to PTC antibiotics and suggests the potential for a wider clinical threat.
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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.