The proposed research focuses on examining a transcription termination system in Gram positive bacteria. This system uses an RNA to control gene expression by binding lysine. Conserved sequence and structural patters has identified a number of genes within the lysine biosynthetic pathway that contain features characteristic of transcription termination systems. These features include competing terminator and anti-terminator structures. Studies done by the Henkin lab have shown that the lysC leader RNA has the ability to directly bind lysine at physiological concentrations (3mM), while discriminating against other products of the pathway. This specificity and high affinity for lysine warrants the investigation of the molecular mechanism of ligand binding. Our approach to understanding the system involves the characterization of mutants with an altered affinity for lysine and lysine analogs. With this work we hope to identify particular residues and contacts important for ligand binding .
|Wilson-Mitchell, Sharnise N; Grundy, Frank J; Henkin, Tina M (2012) Analysis of lysine recognition and specificity of the Bacillus subtilis L box riboswitch. Nucleic Acids Res 40:5706-17|
|Ataide, Sandro F; Wilson, Sharnise N; Dang, Sandy et al. (2007) Mechanisms of resistance to an amino acid antibiotic that targets translation. ACS Chem Biol 2:819-27|