STRUCTURE OF THE A-SITE OF ESCHERICHIA-COLI 16S RIBOSOMAL-RNA COMPLEXED WITH AN AMINOGLYCOSIDE ANTIBIOTIC

Aminoglycoside antibiotics that bind to 30S ribosomal A-site RNA cause misreading of the genetic code and inhibit translocation. The aminogl ycoside antibiotic paromomycin binds specifically to an RNA oligonucle otide that contains the 30S subunit A site, and the solution structure of the RNA-paromomycin complex was determined by nuclear magnetic res onance spectroscopy. The antibiotic binds in the major groove of the m odel A-site RNA within a pocket created by an A-A base pair and a sing le bulged adenine. Specific interactions occur between aminoglycoside chemical groups important for antibiotic activity and conserved nucleo tides in the RNA. The structure explains binding of diverse aminoglyco sides to the ribosome, their specific activity against prokaryotic org anisms, and various resistance mechanisms, and provides insight into r ibosome function.