The effects of the EnvZ histidine kinase inhibitors on the virulence of Shigella flexneri

	The effects of the EnvZ histidine kinase inhibitors on the virulence of Shigella flexneri
	CHEN Mingliang 1; WANG Qi 2; DONG Shengfu 1; QIN Zhiqiang 1; ZHANG Jian 2; HAN Cong 1; SHEN Xu2 ; QU Di 1
刊名	Fudan University Journal of Medical Sciences
	2007
卷号	34 期号:3 页码:317-322
关键词	Shigella flexneri histidine kinase surface plasmon resonance
ISSN号	1672-8467
其他题名	组氨酸蛋白激酶EnvZ抑制剂对福氏志贺菌毒力影响的初步研究
文献子类	Article
英文摘要	Purpose To explore the effects of the EnvZ histidine kinase inhibitors on the virulence of Shigella flexneri. Methods Recombinant S. flexneri SF-EnvZe was cloned into the expression vector pQE30 and was expressed and purified in Escherichia coli system. By using Kinase-Glo^TM Luminescent Kinase assay to screen against the chemical library, compounds which inhibit the autophosphorylation activity of SF-EnvZe were selected as EnvZ inhibitors. The binding affinities of the inhibitors to SF-EnvZe protein were determined by using surface plasmon resonance （SPR） in vitro. The mouse sereny test was used to evaluate the effect of EnvZ inhibitors on the virulence of the Shigella flexneri sf9380. Results Compounds 1, 2, and 3 inhibited the activity of SF-EnvZe autophosphorylation with ICs0 values of （70. 17 5.83）mumol/L, （10. 18 0. 86）mumol/L, and （37.66 9.64）mumol/L, respec- tively. Their high binding affinities to SF-EnvZe were evaluated with Ka values of 4.08 t~mol/L, 3.57 mumol/L, and 2.94mumol/L, respectively. In mouse sereny test, the mice inoculated with sf9380 whichwas treated with compounds 1 and 2 displayed no disease, the group inoculated with sf9380 which was treated with compound 3 displayed a slight conjunctival inflammation （＋）, while the control group inoculated with sf9380 which was treated with dimthyl sulfoxide displayed a severe keratoconjunctival inflammation （＋＋＋）. The minimum effective concentrations of compounds 1, 2, and 3 to release mouse sereny reaction were 12.5 mumol/L, 12.5 mumol/L, and 100 mumol/L, respectively. Conclusions The three EnvZ inhibitors, compounds 1, 2, and 3, can release the the mouse sereny reaction of Shigella flexneri, suggesting that these three EnvZ inhibitors can reduce the virulence of Shigella flexneri.
资助项目	国家重大基础研究专项（973）（2002CB512803）[00000000] ; 国家自然科学基金（3040017,30628001）[00000000] ; 上海市科技发展基金项目（02DJ14002,055407069）[00000000]
WOS研究方向	General & Internal Medicine (provided by Clarivate Analytics)
语种	中文
CSCD记录号	CSCD:2885000
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/268141]
专题	药物化学研究室
作者单位	1.Key Laboratory of Medical Molecular Virology, Ministry of Eeducation and Ministry of Public Health of Peoples＇ Republic of China-Institute of Biomedical Sciences and Institute of Medical Microbiology-Shanghai Medical College, Fudan University, Shanghai 200032, China.; 2.Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
推荐引用方式 GB/T 7714	CHEN Mingliang,WANG Qi,DONG Shengfu,et al. The effects of the EnvZ histidine kinase inhibitors on the virulence of Shigella flexneri[J]. Fudan University Journal of Medical Sciences,2007,34(3):317-322.
APA	CHEN Mingliang.,WANG Qi.,DONG Shengfu.,QIN Zhiqiang.,ZHANG Jian.,...&QU Di.(2007).The effects of the EnvZ histidine kinase inhibitors on the virulence of Shigella flexneri.Fudan University Journal of Medical Sciences,34(3),317-322.
MLA	CHEN Mingliang,et al."The effects of the EnvZ histidine kinase inhibitors on the virulence of Shigella flexneri".Fudan University Journal of Medical Sciences 34.3(2007):317-322.