NMR and molecular modelling studies of the binding of amicetin antibiotic to conserved secondary structural motifs of 23S ribosomal RNAs.

The interaction of a highly conserved secondary structural RNA motif of Halobacterium halobium and Escherichia coli 23S ribosomal RNAs with the peptidyl transferase inhibitor antibiotic amicetin has been investigated by proton NMR spectroscopy and molecular modelling. The NMR spectra of the synthetic 35mer RNA motifs revealed spectral features characteristic of a stable, well folded A-RNA type tertiary conformation, including resolved resonances assigned to unpaired bases located in the middle of the motif strongly implicated in amicetin binding. Addition of amicetin to the 35mer RNA samples was accompanied by significant and discrete changes to the spectra which can be qualitatively interpreted to the changes induced to the local conformation of the RNA motifs arising from the formation of a specific complex with amicetin. These results are also supported by the unconstrained molecular model of RNA-amicetin complex which highlights potential interactions between the two molecular components.