BROAD LIGAND SPECIFICITY OF THE TRANSCRIPTIONAL REGULATOR OF THE BACILLUS-SUBTILIS MULTIDRUG TRANSPORTER BMR

The expression of the Bacillus subtilus multidrug-efflux transporter E mr can be induced by two of its structurally dissimilar substrates, rh odamine 6G and tetraphenylphosphonium, through their direct interactio n with the transcriptional regulator BmrR (Ahmed et al., J. Biol., Che m. 269, 28506). Here, by screening a chemical Library, we identified f our additional ligands of BmrR inducing Bmr expression at micromolar c oncentrations. BmrR ligands, although sharing a positive charge and mo derate hydrophobicity, are structurally very diverse. At the same time , not all hydrophobic positively charged compounds, including many str uctural analogs of the inducers, induce Bmr expression, thus suggestin g that local chemical interactions and not merely physical properties of the ligands are important for their recognition by BmrR. These resu lts confirm that this soluble protein, like the membrane transporter i t regulates, has a uniquely broad substrate specificity. (C) 1997 Acad emic Press.