BINDING OF NEOMYCIN-CLASS AMINOGLYCOSIDE ANTIBIOTICS TO THE A-SITE OF16-S RIBOSOMAL-RNA

Aminoglycoside antibiotics that bind to ribosomal RNA in the aminoacyl -tRNA site (A-site) cause misreading of the genetic code and inhibit t ranslocation. We have recently solved the structure of an A-site RNA-p aromomycin complex. The structure suggested that rings I and II, commo n to all aminoglycosides that bind to the A-site, are the minimum moti f for specific ribosome binding to affect translation. This hypothesis was tested biochemically and with a detailed comparative NMR study of interaction of the aminoglycosides paromomycin, neomycin, ribostamyci n, and neamine with the A-site RNA. Our NMR data show that rings I and II of neomycin-class aminoglycosides are sufficient to confer specifi city to the binding of the antibiotics to the model A-site RNA. Neomyc in, paromomycin, ribostamycin and neamine bind in the major groove of the A-site RNA in a unique binding pocket formed by non-canonical base pairs and a bulged nucleotide. Similar NMR properties of the RNA and the diverse antibiotics within the different complexes formed with neo mycin, paromomycin, ribostamycin and neamine suggest similar structure s for these complexes. (C) 1998 Academic Press Limited.