Structural analysis of base substitutions in Thermus thermophilus 16S rRNA conferring streptomycin resistance.
Publication Type:Journal Article
Source:Antimicrob Agents Chemother, Volume 58, Issue 8, p.4308-17 (2014)
Keywords:Anti-Bacterial Agents, Base Pairing, Base Sequence, Binding Sites, Crystallography, X-Ray, Drug Resistance, Bacterial, Hydrogen Bonding, Models, Molecular, Molecular Sequence Data, Nucleic Acid Conformation, Point Mutation, Protein Biosynthesis, Ribosomal Proteins, Ribosome Subunits, Small, Bacterial, RNA, Ribosomal, 16S, Streptomycin, Thermus thermophilus
<p>Streptomycin is a bactericidal antibiotic that induces translational errors. It binds to the 30S ribosomal subunit, interacting with ribosomal protein S12 and with 16S rRNA through contacts with the phosphodiester backbone. To explore the structural basis for streptomycin resistance, we determined the X-ray crystal structures of 30S ribosomal subunits from six streptomycin-resistant mutants of Thermus thermophilus both in the apo form and in complex with streptomycin. Base substitutions at highly conserved residues in the central pseudoknot of 16S rRNA produce novel hydrogen-bonding and base-stacking interactions. These rearrangements in secondary structure produce only minor adjustments in the three-dimensional fold of the pseudoknot. These results illustrate how antibiotic resistance can occur as a result of small changes in binding site conformation. </p>