靶向双组分信号转导：一种新型药物发现系统。

Targeting two-component signal transduction: a novel drug discovery system.

作者信息

Okada Ario, Gotoh Yasuhiro, Watanabe Takafumi, Furuta Eiji, Yamamoto Kaneyoshi, Utsumi Ryutaro

机构信息

Department of Bioscience, Kinki University, Nara, Japan.

出版信息

Methods Enzymol. 2007;422:386-95. doi: 10.1016/S0076-6879(06)22019-6.

DOI:10.1016/S0076-6879(06)22019-6

PMID:17628150

Abstract

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.

摘要

我们开发了两种筛选系统，用于分离靶向细菌双组分信号转导的抑制剂：（1）一种差异生长测定法，使用枯草芽孢杆菌的温度敏感型yycF突变体（CNM2000），该突变体对组氨酸激酶抑制剂超敏感；（2）一种高通量遗传系统，用于靶向细菌双组分信号转导所必需的组氨酸激酶的同二聚化。通过使用这些方法，我们已经能够鉴定出各种类型的抑制剂，它们以不同的作用模式阻断组氨酸激酶的自磷酸化。