Enzymatic characterization and inhibitor discovery of a new cystathionine gamma-synthase from Helicobacter pylori
文献类型：期刊论文
| 作者 | Kong, Yunhua1; Wu, Dalei1; Bai, Haiyun1; Han, Cong1; Chen, Jing1 ; Chen, Lili1; Hu, Lihong1,2; Jiang, Hualiang1,2; Shen, Xu1,2
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| 刊名 | JOURNAL OF BIOCHEMISTRY
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| 出版日期 | 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 |
| WOS记录号 | WOS:000254996900007 |
| 出版者 | OXFORD UNIV PRESS |
| 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. |
入库方式： OAI收割
来源：上海药物研究所
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