Summary
Bacterial signal transduction systems can be used as drug targets. The signal transduction targets fall into two groups–-sensor kinases and response regulators. Previously reported studies describe hits that were thought to inactivate sensor kinases but on closer examination were found to act elsewhere instead; a possible reason for this is that full-length sensor kinases are integral membrane proteins whose activity might reflect interaction with the cell membrane or with membrane components. We describe a model system that instead is based on the interaction between a test compound and a response regulator in a homogeneous phase reaction. In this system, response regulator-DNA complex formation and its inhibition by a test compound are measured by fluorescence polarization. The model system should be readily adaptable to drug discovery based on other bacterial two-component s transduction systems.
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Acknowledgments
We thank F. M. Hoffmann for access to a fluorometer, supported by the University of Wisconsin Clinical Cancer Center.
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Erickson, M.G., Ulijasz, A.T., Weisblum, B. (2008). Screening for Compounds That Affect the Interaction Between Bacterial Two-Component Signal Transduction Response Regulator Protein and Cognate Promoter DNA. In: Champney, W.S. (eds) New Antibiotic Targets. Methods In Molecular Medicine™, vol 142. Humana Press. https://doi.org/10.1007/978-1-59745-246-5_17
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DOI: https://doi.org/10.1007/978-1-59745-246-5_17
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