Molecular Recognition by Glycoside Pseudo Base Pairs and Triples in an Apramycin-RNA Complex

摘要

The ribosome and its RNA components are targets for a diverse set of antibiotics, including the natural aminoglycosides, macrolides, and tetracyclins and the synthetic oxazolidinones, all of which interfere with bacterial protein synthesis.[1], [2] Crystallographic analyses of ribosomal subunits and domains thereof in complex with antibiotics have demonstrated that the natural products interact almost exclusively with ribosomal RNA components (rRNA),[3] a result that lends support to earlier biochemical findings[4], [5] and underlines the importance of RNA as a drug target.[6] Aminoglycoside antibiotics bind to 16S rRNA near the mRNA decoding site and thereby decrease the fidelity of translation by lowering the energetic cost of a conformational transition in the ribosome that is required for the discrimination between near-cognate and cognate tRNAs.[7], [8] Insight into the molecular recognition of the decoding site by antibiotic ligands and the mechanics of translational fidelity are emerging from three-dimensional structures of aminoglycosides in complex with decoding-site oligonucleotides and whole 30S ribosomal subunits.