Enzymatic characterization and inhibitor discovery of a new cystathionine gamma-synthase from Helicobacter pylori

doi:10.1093/jb/mvm194

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第三研究室

	Enzymatic characterization and inhibitor discovery of a new cystathionine gamma-synthase from Helicobacter pylori
	Kong, Yunhua 1; Wu, Dalei 1; Bai, Haiyun 1; Han, Cong 1; Chen, Jing1 ; Chen, Lili1 ; Hu, Lihong 1,2; Jiang, Hualiang1,2 ; Shen, Xu1,2
刊名	JOURNAL OF BIOCHEMISTRY
	2008-01
卷号	143 期号:1 页码:59-68
关键词	cystathionine gamma-synthase Helicobacter pylori inhibitor inhibitor type minimum inhibition concentration transsulfuration
ISSN号	0021-924X
DOI	10.1093/jb/mvm194
文献子类	Article
英文摘要	Cystathionine gamma-synthase (CGS) catalyses the first step of the transsulfuration pathway that converts L-cysteine to L-homocysteine in bacteria, whereas this pathway is absent in human. In this report, we identified a new metB gene from Helicobacter pylori strain SS1, and the recombinant H. pylori Cystathionine,gamma-synthase (HpCGS) was successfully cloned, expressed and purified in Escherichia coli system. Enzymatic study of HpCGS indicated that the Km and k(cat)/K(m) values against the substrate O-succinyl-L-homoserine (L-OSHS) were 3.02mM and 98.7M(-1)s(-1), respectively. Moreover, four natural products (alpha-lapachone, 9-hydroxy-alpha-lapachone, Paulownin and Yangambin, Fig. 1) were discovered to demonstrate inhibitory activities against HpCGS with IC(50) values of 11 +/- 3, 9 +/- 1, 19 +/- 2 and 27 +/- 6 mu M, respectively. All these four inhibitors prevent the binding of L-OSHS to HpCGS in a non-competitive fashion. In vitro antibacterial assays further indicated that these four discovered compounds could highly inhibit the growth of H. pylori and exhibited strong inhibitory specificity against H. pylori related to E. coli.
WOS关键词	ESCHERICHIA-COLI ; METHIONINE BIOSYNTHESIS ; NICOTIANA-TABACUM ; CRYSTAL-STRUCTURE ; AMINO-ACIDS ; PURIFICATION ; CLONING ; INTERMEDIATE ; ELIMINATION ; ERADICATION
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	OXFORD UNIV PRESS
WOS记录号	WOS:000254996900007
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/273062]
专题	药理学第三研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Shen, Xu
作者单位	1.Chinese Acad Sci, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai Inst Materia Med, Shanghai 201203, Peoples R China; 2.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China
推荐引用方式 GB/T 7714	Kong, Yunhua,Wu, Dalei,Bai, Haiyun,et al. Enzymatic characterization and inhibitor discovery of a new cystathionine gamma-synthase from Helicobacter pylori[J]. JOURNAL OF BIOCHEMISTRY,2008,143(1):59-68.
APA	Kong, Yunhua.,Wu, Dalei.,Bai, Haiyun.,Han, Cong.,Chen, Jing.,...&Shen, Xu.(2008).Enzymatic characterization and inhibitor discovery of a new cystathionine gamma-synthase from Helicobacter pylori.JOURNAL OF BIOCHEMISTRY,143(1),59-68.
MLA	Kong, Yunhua,et al."Enzymatic characterization and inhibitor discovery of a new cystathionine gamma-synthase from Helicobacter pylori".JOURNAL OF BIOCHEMISTRY 143.1(2008):59-68.