Aminoglycoside binding displaces a divalent metal ion in a tRNA-neomycin Bcomplex

Aminoglycosides bind to RNA and interfere with its function, and it has bee n suggested that aminoglycoside binding to RNA displaces essential divalent metal ions. Here we demonstrate that addition of various aminoglycosides i nhibited Pb2+-induced cleavage of yeast tRNA(Phe), Cocrystallization of yea st tRNA(Phe) and an aminoglycoside, neomycin B, resulted in crystals that d iffracted to 2.6 Angstrom and the structure of the complex was solved by mo lecular replacement, The structure shows that the neomycin B binding site o verlaps with known divalent metal ion binding sites in yeast tRNA(Phe), pro viding direct evidence for the hypothesis that aminoglycosides displace met al ions. Additionally, the neomycin B binding site overlaps with major dete rminants for Escherichia coli phenylalanyl-tRNA-synthetase, Here we present data demonstrating that addition of neomycin B inhibited aminoacylation of E. coli tRNA(Phe) in the mid muM range. Given that aminoglycoside and meta l ion binding sites overlap, we discuss that aminoglycosides can be conside red as 'metal mimics'.