ArticleNucleic acids research2007
Engineering the rRNA decoding site of eukaryotic cytosolic ribosomes in bacteria.
Article in Nucleic acids research, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 79 citations in OpenAlex.
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- Structure-Activity Relationships for 5'' Modifications of 4,5-Aminoglycoside Antibiotics.ChemMedChem · 2022Article
- Influence of ring size in conformationally restricted ring I analogs of paromomycin on antiribosomal and antibacterial activity.RSC medicinal chemistry · 2021Article
- Synthesis and Antibacterial Activity of Propylamycin Derivatives Functionalized at the 5''- and Other Positions with a View to Overcoming Resistance Due to Aminoglycoside Modifying Enzymes.ACS infectious diseases · 2021Article
- An Advanced Apralog with Increased in vitro and in vivo Activity toward Gram-negative Pathogens and Reduced ex vivo Cochleotoxicity.ChemMedChem · 2021Article
- Predictive Analysis of the Side Chain Conformation of the Higher Carbon Sugars: Application to the Preorganization of the Aminoglycoside Ring 1 Side Chain for Binding to the Bacterial Ribosomal Decoding A Site.The Journal of organic chemistry · 2020Article
- Aminoglycosides: Time for the Resurrection of a Neglected Class of Antibacterials?ACS infectious diseases · 2020Article
- Apralogs: Apramycin 5-Journal of the American Chemical Society · 2020Article
- Modification at the 2'-Position of the 4,5-Series of 2-Deoxystreptamine Aminoglycoside Antibiotics To Resist Aminoglycoside Modifying Enzymes and Increase Ribosomal Target Selectivity.ACS infectious diseases · 2019Article
- A dual role of the ribosome-bound chaperones RAC/Ssb in maintaining the fidelity of translation termination.Nucleic acids research · 2019Article
- Synthesis, ribosomal selectivity, and antibacterial activity of netilmicin 4'-derivatives.MedChemComm · 2019Article
- In vitro activity of apramycin against multidrug-, carbapenem- and aminoglycoside-resistant Enterobacteriaceae and Acinetobacter baumannii.The Journal of antimicrobial chemotherapy · 2019Article
- Synthesis of saccharocin from apramycin and evaluation of its ribosomal selectivity.MedChemComm · 2019Article
- Design, Multigram Synthesis, and in Vitro and in Vivo Evaluation of Propylamycin: A Semisynthetic 4,5-Deoxystreptamine Class Aminoglycoside for the Treatment of Drug-Resistant Enterobacteriaceae and Other Gram-Negative Pathogens.Journal of the American Chemical Society · 2019Article
- Mechanistic insights into the slow peptide bond formation with D-amino acids in the ribosomal active site.Nucleic acids research · 2019Article
- Mutant MRPS5 affects mitoribosomal accuracy and confers stress-related behavioral alterations.EMBO reports · 2018Article
- Aminoglycoside Revival: Review of a Historically Important Class of Antimicrobials Undergoing Rejuvenation.EcoSal Plus · 2018Review
- Effects of the 1- N-(4-Amino-2 S-hydroxybutyryl) and 6'- N-(2-Hydroxyethyl) Substituents on Ribosomal Selectivity, Cochleotoxicity, and Antibacterial Activity in the Sisomicin Class of Aminoglycoside Antibiotics.ACS infectious diseases · 2018Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Structural and genetic studies on prokaryotic ribosomes have provided important insights into fundamental aspects of protein synthesis and translational control and its interaction with ribosomal drugs. Comparable mechanistic studies in eukaryotes are mainly hampered by the absence of both high-resolution crystal structures and efficient genetic models. To study the interaction of aminoglycoside antibiotics with selected eukaryotic ribosomes, we replaced the bacterial drug binding site in 16S rRNA with its eukaryotic counterpart, resulting in bacterial hybrid ribosomes with a fully functional eukaryotic rRNA decoding site. Cell-free translation assays demonstrated that hybrid ribosomes carrying the rRNA decoding site of higher eukaryotes show pronounced resistance to aminoglycoside antibiotics, equivalent to that of rabbit reticulocyte ribosomes, while the decoding sites of parasitic protozoa show distinctive drug susceptibility. Our findings suggest that phylogenetically variable components of the ribosome, other than the rRNA-binding site, do not affect aminoglycoside susceptibility of the protein-synthesis machinery. The activities of the hybrid ribosomes indicate that helix 44 of the rRNA decoding site behaves as an autonomous domain, which can be exchanged between ribosomes of different phylogenetic domains for study of function.
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