Related Experiment Video
Updated: Jul 16, 2026

Dual DNA Rulers to Study the Mechanism of Ribosome Translocation with Single-Nucleotide Resolution
Published on: July 8, 2019
Defining the molecular forces that determine the impact of neomycin on bacterial protein synthesis: importance of the
Christopher M Barbieri1, Malvika Kaul, Melanie Bozza-Hingos
1UMDNJ-Robert Wood Johnson Medical School, Department of Pharmacology, Piscataway, NJ 08854-5635, USA.
Abstract:
2-Deoxystreptamine (2-DOS) aminoglycosides exert their antibiotic actions by binding to the A site of the 16S rRNA and interfering with bacterial protein synthesis. However, the molecular forces that govern the antitranslational activities of aminoglycosides are poorly understood. Here, we describe studies aimed at elucidating these molecular forces. In this connection, we compare the bactericidal, antitranslational, and rRNA binding properties of the 4,5-disubstituted 2-DOS aminoglycoside neomycin (Neo) and a conformationally restricted analog of Neo (CR-Neo) in which the 2'-nitrogen atom is covalently conjugated to the 5''-carbon atom. The bactericidal potency of Neo exceeds that of CR-Neo, with this enhanced antibacterial activity reflecting a correspondingly enhanced antitranslational potency. Time-resolved fluorescence anisotropy studies suggest that the enhanced antitranslational potency of Neo relative to that of CR-Neo is due to a greater extent of drug-induced reduction in the mobilities of the nucleotides at positions 1492 and 1493 of the rRNA A site. Buffer- and salt-dependent binding studies, coupled with high-resolution structural information, point to electrostatic contacts between the 2'-amino functionality of Neo and the host rRNA as being an important modulator of 1492 and 1493 base mobilities and therefore antitranslational activities.
Related Concept Videos
Inhibitors of Bacterial Protein Synthesis
Nucleic Acid Structure
DNA Structure
DNA has a double-helix structure. The...
Coordination of Gene Expression Processes in Bacteria
Inhibitors of Gram-positive Cell Wall Synthesis
Types of RNA
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
Improving Translational Accuracy

