Thursday, August 14, 2008 - 9:00 AM
S155
The regulation of life by small molecule/transcription factor interactions
Justin R. Nodwell, Leslie Cuthbertson, Sang Kyun Ahn, Kapil Tahlan, Ye Xu, and Leigh Ann Roddick. Biochemistry and Biomedical Sciences, McMaster University, Health Sciences Centre, 1200 Main Street W, Hamilton, ON L8N 3Z5, Canada
Many biological processes are controlled by small molecules such as pheromones, antibiotics or toxins. TetR, which regulates tetracycline resistance, mediates such a response. tetR is adjacent to and divergent from tetA which encodes a tetracycline efflux pump: the promoters for both are in the intervening DNA. TetR binds the promoters and shuts them off. Tetracycline interacts with the C-terminal domain of TetR causing release and tetA expression, thereby conferring tetracycline resistance. There are >6000 tetR-like genes in the sequenced genomes and our evidence suggests that most of them regulate adjacent genes. As a result of this arrangement, it is easy to identify putative repressor binding sites. Structural data suggests that most or all TetR-like-proteins (TLPs) interact with small molecule ligands. Identifying these ligands is critical to understanding this enormous gene family as in most cases the ligand of the TLP is related or identical to the substrate of the target gene product. We have established bioinformatic and high throughput screening technologies that will enable us to identify ligands for many TLPs. We are focusing on the >150 TLPs encoded by the model antibiotic-producer Streptomyces coelicolor. The targets of these transcription factors include putative antibiotic resistance genes, enzymes, kinases and a very large number of proteins of unknown function. Our initial work has focused on ActR, which regulates the export of the antibiotic actinorhodin, but we are most interested in identifying ligands for TLPs that control production of proteins of unknown function.
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See more of The Annual Meeting and Exhibition 2008 (August 10 - 14, 2008)