SPECIFICITY OF AMINOGLYCOSIDE ANTIBIOTICS FOR THE A-SITE OF THE DECODING REGION OF RIBOSOMAL-RNA

Background: Aminoglycoside antibiotics bind to the A-site of the decod ing region of 16S RNA in the bacterial ribosome, an interaction that i s probably responsible for their activity, A detailed study of the spe cificity of aminoglycoside binding to A-site RNA would improve our und erstanding of their mechanism of antibiotic activity, Results: We have studied the binding specificity of several aminoglycosides with model RNA sequences derived from the 16S ribosomal A-site using surface pla smon resonance, The 4,5-linked (neomycin) class of aminoglycosides sho wed specificity for wild-type A-site sequences, but the 4,6-linked cla ss (kanamycins and gentamicins), generally showed poor specificity for the same sequences, Methylation of a cytidine in the target RNA, as f ound in the Escherichia coli ribosome, had negligible effects on amino glycoside binding. Conclusions: Although both 4,5- and 4,6-linked amin oglycosides target the same ribosomal site, they appear to bind and ef fect antibiotic activity in different manners, The aminoglycosides mig ht recognize different RNA conformations or the interaction might invo lve different RNA tertiary structures that are not equally sampled in our ribosome-free model. These results imply that models of ribosomal RNA must be carefully designed if the data are expected to accurately reflect biological activity.