Targeting two-component signal transduction: a novel drug discovery system.
We have developed two screening systems for isolating inhibitors that target bacterial two-component signal transduction: (1) a differential growth assay using a temperature-sensitive yycF mutant (CNM2000) of Bacillus subtilis, which is supersensitive to histidine kinase inhibitors, and (2) a high-throughput genetic system for targeting the homodimerization of histidine kinases essential for the bacterial two-component signal transduction. By using these methods, we have been able to identify various types of inhibitors that block the autophosphorylation of histidine kinases with different modes of actions.
Okada
Ario
A
Department of Bioscience, Kinki University, Nara, Japan.
Gotoh
Yasuhiro
Y
Watanabe
Takafumi
T
Furuta
Eiji
E
Yamamoto
Kaneyoshi
K
Utsumi
Ryutaro
R
D001412:Bacillus subtilis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D001426:Bacterial Proteins / Q000235:genetics*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D009154:Mutation; D010957:Plasmids; D015398:Signal Transduction
D001426:Bacterial Proteins