Binding of neomycin-class aminoglycoside antibiotics to the A-site of 16 S rRNA.
Aminoglycoside antibiotics that bind to ribosomal RNA in the aminoacyl-tRNA site (A-site) cause misreading of the genetic code and inhibit translocation. We have recently solved the structure of an A-site RNA-paromomycin complex. The structure suggested that rings I and II, common to all aminoglycosides that bind to the A-site, are the minimum motif 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, ribostamycin, and neamine with the A-site RNA. Our NMR data show that rings I and II of neomycin-class aminoglycosides are sufficient to confer specificity to the binding of the antibiotics to the model A-site RNA. Neomycin, 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 neomycin, paromomycin, ribostamycin and neamine suggest similar structures for these complexes.
Fourmy
D
D
Center for Molecular Biology of RNA, University of California, Santa Cruz, CA 95064, USA.
Recht
M I
MI
Puglisi
J D
JD
D000900:Anti-Bacterial Agents / Q000378:metabolism*; D001665:Binding Sites; D002240:Carbohydrate Sequence; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009355:Neomycin / Q000378:metabolism*; D012336:RNA, Ribosomal, 16S / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D012336:RNA, Ribosomal, 16S; D009355:Neomycin