Targeting protein homodimerization: A novel drug discovery system
- 11 March 2005
- journal article
- Published by Wiley in FEBS Letters
- Vol. 579 (10), 2065-2070
- https://doi.org/10.1016/j.febslet.2005.02.056
Abstract
To identify a novel class of antibiotics, we have developed a high-throughput genetic system for targeting the homodimerization (HD system) of histidine kinase (HK), which is essential for a bacterial signal transduction system (two-component system, TCS). By using the HD system, we screened a chemical library and identified a compound, I-8-15 (1-dodecyl-2-isopropylimidazole), that specifically inhibited the dimerization of HK encoded by the YycG gene of Staphylococcus aureus and induced concomitant bacterial cell death. I-8-15 also showed antibacterial activity against MRSA (methicillin-resistant S. aureus) and VRE (vancomycin-resistant Enterococcus faecalis) with MICs at 25 and 50 microg/ml, respectively.Keywords
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