Structural origins of gentamicin antibiotic action

Aminoglycoside antibiotics that bind to the ribosomal A site cause misreadi ng of the genetic code and inhibit translocation, The clinically important aminoglycoside, gentamicin C, is a mixture of three components. Binding of each gentamicin component to the ribosome and to a model RNA oligonucleotid e was studied biochemically and the structure of the RNA complexed to genta micin Cia was solved using magnetic resonance nuclear spectroscopy. Gentami cin Cia binds in the major groove of the RNA. Rings I and II of gentamicin direct specific RNA-drug interactions. Ring III of gentamicin, which distin guishes this subclass of aminoglycosides, also directs specific RNA interac tions with conserved base pairs. The structure leads to a general model for specific ribosome recognition by aminoglycoside antibiotics and a possible mechanism for translational inhibition and miscoding. This study provides a structural rationale for chemical synthesis of novel aminoglycosides.