Ribosomal RNA Recognition by Aminoglycoside Antibiotics

Abstract

2-Deoxystreptamine (2-DOS) aminoglycosides are a family of structurally related broad-spectrum antibiotics that are used widely in the clinic. Their antibiotic activities are ascribed to their abilities to bind a highly conserved sequence (termed the A site) in the 16S rRNA of the 30S ribosomal subunit and interfere with protein synthesis. The aminoglycosides represent a paradigm for both drug–RNA and drug–ribosome interactions, and information gleaned from their study has relevance with regard to other RNA- and ribosome-directed drugs of acute clinical importance. This contribution provides an integrated overview of structural and thermodynamic studies of the rRNA binding of aminoglycosides. The results of these studies have enhanced our understanding of the molecular forces that govern aminoglycoside recognition of the rRNA A site, and underlie the mechanism and specificity of action of these drugs. Such knowledge provides the type of predictive capabilities that are essential for the devlopment of a rational basis for future drug design strategies.