Fluorescence resonance energy transfer studies of aminoglycoside binding to a T box antiterminator RNA

The T box transcription antitermination mechanism is found in many Gram-positive bacteria. The T box genes are typically tRNA synthetase, amino acid biosynthesis, and amino acid transport genes that have a common transcriptional control mechanism in which a unique RNA–RNA interaction occurs between an uncharged tRNA and the 5′ leader region of the nascent mRNA, leading to antitermination of transcription. The tRNA binds the mRNA in at least two regions: the specifier sequence and the antiterminator. If the latter interaction does not occur, then transcription is terminated. The binding of eight different aminoglycosides to a model of the Bacillus subtilis tyrS T box antiterminator RNA has been studied using fluorescence resonance energy transfer. The observed single-site binding dissociation constants were in the low to mid micromolar range. The structure–activity relationship of aminoglycoside binding indicates that selective binding of small molecules to T box antiterminator RNA can be achieved.