ArticleAntimicrobial agents and chemotherapy2005
Analysis of the contribution of individual substituents in 4,6-aminoglycoside-ribosome interaction.
Article in Antimicrobial agents and chemotherapy, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 64 citations in OpenAlex.
- Trends in the Antibiotic Resistance of Non-Tuberculous Mycobacteria in Iran: A Systematic Review and Meta-Analysis.Iranian journal of public health · 2023Review
- Drug susceptibility distributions ofAntimicrobial agents and chemotherapy · 2023Article
- Phenotype of Mrps5-Associated Phylogenetic Polymorphisms Is Intimately Linked to Mitoribosomal Misreading.International journal of molecular sciences · 2022Article
- Structural Bases for the Fitness Cost of the Antibiotic-Resistance and Lethal Mutations at Position 1408 of 16S rRNA.Molecules (Basel, Switzerland) · 2019Article
- Roles of specific aminoglycoside-ribosome interactions in the inhibition of translation.RNA (New York, N.Y.) · 2019Article
- Mutant MRPS5 affects mitoribosomal accuracy and confers stress-related behavioral alterations.EMBO reports · 2018Article
- Antimicrobial Activity, AME Resistance, and A-Site Binding Studies of Anthraquinone-Neomycin Conjugates.ACS infectious diseases · 2017Article
- Evidence That Antibiotics Bind to Human Mitochondrial Ribosomal RNA Has Implications for Aminoglycoside Toxicity.The Journal of biological chemistry · 2015Article
- Tobramycin Variants with Enhanced Ribosome-Targeting Activity.Chembiochem : a European journal of chemical biology · 2015Article
- Article
- New trends in aminoglycosides use.MedChemComm · 2014Article
- Structure-activity relationships among the kanamycin aminoglycosides: role of ring I hydroxyl and amino groups.Antimicrobial agents and chemotherapy · 2012Article
- Dissociation of antibacterial activity and aminoglycoside ototoxicity in the 4-monosubstituted 2-deoxystreptamine apramycin.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- SMRT compounds correct nonsense mutations in primary immunodeficiency and other genetic models.Annals of the New York Academy of Sciences · 2012Review
- Phylogenetic sequence variations in bacterial rRNA affect species-specific susceptibility to drugs targeting protein synthesis.Antimicrobial agents and chemotherapy · 2011Article
- Genetic analysis of new 16S rRNA mutations conferring aminoglycoside resistance in Mycobacterium abscessus.The Journal of antimicrobial chemotherapy · 2011Article
- Understanding the origins of bacterial resistance to aminoglycosides through molecular dynamics mutational study of the ribosomal A-site.PLoS computational biology · 2011Article
- Genetic reconstruction of protozoan rRNA decoding sites provides a rationale for paromomycin activity against Leishmania and Trypanosoma.PLoS neglected tropical diseases · 2011Article
- Mutations in 23S rRNA at the peptidyl transferase center and their relationship to linezolid binding and cross-resistance.Antimicrobial agents and chemotherapy · 2010Article
- Positional and neighboring base pair effects on the thermodynamic stability of RNA single mismatches.Biochemistry · 2010Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The 4,6-disubstituted 2-deoxystreptamines interfere with protein biosynthesis by specifically targeting the ribosomal A site. These drugs show subtle variations in the chemical groups of rings I, II, and III. In the present study we used site-directed mutagenesis to generate mutant strains of Mycobacterium smegmatis mc(2)155 SMR5 DeltarrnB with mutations in its single rRNA allele, rrnA. This genetic procedure gives rise to strains carrying homogeneous populations of mutant ribosomes and was used to study the contribution of individual chemical substituents to the binding of 4,6-disubstituted aminoglycosides. X-ray crystal structures of geneticin and tobramycin complexed to oligonucleotides containing the minimal bacterial ribosomal A site were used for interpretation of MICs determined for a panel of 4,6-aminoglycosides, including tobramycin, kanamycin A, kanamycin B, amikacin, gentamicin, and geneticin. Surprisingly, the considerable differences present within ring III did not seem to alter the interaction of the drug with the ribosome, as determined by site-directed mutagenesis of the A site. In contrast, subtle variations in ring I significantly influenced binding: (i) a 4'-hydroxyl moiety participates in the proper drug target interaction; and (ii) a 2'-amino group contributes an additional positive charge to ring I, making the drug less susceptible to any kind of sequence alteration within the decoding site, most notably, to conformational changes induced by transversion of U1495 to 1495A. The 4-amino-2-hydroxyl-1-oxobutyl extension at position 1 of ring II of amikacin provides an additional anchor and renders amikacin less dependent on the structural conformation of nucleotide U1406 compared to the dependencies of other kanamycins. Overall, the set of interactions forming the complex between drug substituents and nucleotides of the A site constitutes a network in which the interactions can partly compensate for each other when they are disrupted.
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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.