Structure of the A Site of Escherichia coli 16 S Ribosomal RNA Complexed with an Aminoglycoside Antibiotic

• DOI: 10.1126/science.274.5291.1367
• Publication Date: 2002-07-27T09:37:46Z
• Authors: Dominique Fourmy; Michael I. Recht; Scott C. Blanchard; Joseph D. Puglisi
• Keywords: Models, Molecular; Base Composition; 0303 health sciences; Binding Sites; Magnetic Resonance Spectroscopy; Oligoribonucleotides; Paromomycin; Hydrogen Bonding; Methylation; Anti-Bacterial Agents; 3. Good health; RNA, Bacterial; 03 medical and health sciences; RNA, Ribosomal, 16S; Escherichia coli; Nucleic Acid Conformation; Ribosomes

Aminoglycoside antibiotics that bind to 30 S ribosomal A-site RNA cause misreading of the genetic code and inhibit translocation. The aminoglycoside antibiotic paromomycin binds specifically to an RNA oligonucleotide that contains the 30 S subunit A site, and the solution structure of the RNA-paromomycin complex was determined by nuclear magnetic resonance spectroscopy. The antibiotic binds in the major groove of the model A-site RNA within a pocket created by an A-A base pair and a single bulged adenine. Specific interactions occur between aminoglycoside chemical groups important for antibiotic activity and conserved nucleotides in the RNA. The structure explains binding of diverse aminoglycosides to the ribosome, their specific activity against prokaryotic organisms, and various resistance mechanisms, and provides insight into ribosome function.