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Targeting protein homodimerization: A novel drug discovery system
Author(s) -
Furuta Eiji,
Yamamoto Kaneyoshi,
Tatebe Daisuke,
Watabe Kounosuke,
Kitayama Takashi,
Utsumi Ryutaro
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.02.056
Subject(s) - enterococcus faecalis , staphylococcus aureus , microbiology and biotechnology , vancomycin , two component regulatory system , chemistry , drug discovery , methicillin resistant staphylococcus aureus , antibiotics , bacteria , biology , gene , biochemistry , genetics , mutant
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 μg/ml, respectively.