Crystal structure and enzymatic characterization of thymidylate synthase X from Helicobacter pylori strain SS1
文献类型：期刊论文
| 作者 | Wang, Kuifeng; Wang, Qi; Chen, Jing ; Chen, Lili; Jiang, Hualiang; Shen, Xu
|
| 刊名 | PROTEIN SCIENCE
 |
| 出版日期 | 2011-08 |
| 卷号 | 20期号:8页码:1398-1410 |
| 关键词 | thymidylate synthase Helicobacter pylori thymidylate synthase ThyA |
| ISSN号 | 0961-8368 |
| DOI | 10.1002/pro.668 |
| 文献子类 | Article |
| 英文摘要 | Thymidylate synthase X (ThyX) catalyzes the methylation of dUMP to form dTMP in bacterial life cycle and is regarded as a promising target for antibiotics discovery. Helicobacter pylori is a human pathogen associated with a number of human diseases. Here, we cloned and purified the ThyX enzyme from H. pylori SS1 strain (HpThyX). The recombinant HpThyX was discovered to exhibit the maximum activity at pH 8.5, and K-m values of the two substrates dUMP and CH(2)H(4)folate were determined to be 15.3 +/- 1.25 mu M and 0.35 +/- 0.18 mM, respectively. The analyzed crystal structure of HpThyX with the cofactor FAD and the substrate dUMP (at 2.31 angstrom) revealed that the enzyme was a tetramer bound to four dUMP and four FAD molecules. Different from the catalytic feature of the classical thymidylate synthase (ThyA), N5 atom of the FAD functioned as a nucleophile in the catalytic reaction instead of Ser84 and Ser85 residues. Our current work is expected to help better understand the structural and enzymatic features of HpThyX thus further providing valuable information for anti-H. pylori inhibitor discovery. |
| WOS关键词 | CATALYTIC MECHANISM ; COMPLEMENTING PROTEIN ; FUNCTIONAL-ANALYSIS ; FLAVIN ; THYX ; BIOSYNTHESIS ; ERADICATION ; CLONING |
| 资助项目 | State Key Program of Basic Research of China[2010CB912501] ; State Key Program of Basic Research of China[2009CB918502] ; National Natural Science Foundation of China[30925040] ; National Natural Science Foundation of China[10979072] ; Foundation of Chinese Academy of Sciences[KSCX2-YW-R-168] ; Foundation of Chinese Academy of Sciences[KSCX1-YW-02-2] |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000293137300008 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278460]  |
| 专题 | 药物安全性评价中心 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 药理学第三研究室 |
| 通讯作者 | Chen, Jing |
| 作者单位 | Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Kuifeng,Wang, Qi,Chen, Jing,et al. Crystal structure and enzymatic characterization of thymidylate synthase X from Helicobacter pylori strain SS1[J]. PROTEIN SCIENCE,2011,20(8):1398-1410. |
| APA | Wang, Kuifeng,Wang, Qi,Chen, Jing,Chen, Lili,Jiang, Hualiang,&Shen, Xu.(2011).Crystal structure and enzymatic characterization of thymidylate synthase X from Helicobacter pylori strain SS1.PROTEIN SCIENCE,20(8),1398-1410. |
| MLA | Wang, Kuifeng,et al."Crystal structure and enzymatic characterization of thymidylate synthase X from Helicobacter pylori strain SS1".PROTEIN SCIENCE 20.8(2011):1398-1410. |
入库方式： OAI收割
来源：上海药物研究所
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