title: Targeting protein homodimerization: a novel drug discovery system.
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.
authors.affiliation: Department of Bioscience and Biotechnology, Graduate School of Agriculture, Kinki University, 3327-204 Nakamachi, Nara 631-8505, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Furuta
authors.forename: Kaneyoshi
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tatebe
authors.forename: Kounosuke
authors.initials: K
authors.lastname: Watabe
authors.forename: Takashi
authors.initials: T
authors.lastname: Kitayama
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Utsumi
mesh_terms: D001483:Base Sequence; D017931:DNA Primers; D019281:Dimerization; D015195:Drug Design; D000071677:Histidine Kinase; D011494:Protein Kinases / Q000737:chemistry; D011506:Proteins / Q000737:chemistry*
chemical_list: D017931:DNA Primers; D011506:Proteins; D011494:Protein Kinases; D000071677:Histidine Kinase