Three flavonoids targeting the beta-hydroxyacyl-acyl carrier protein dehydratase from Helicobacter pylori: Crystal structure characterization with enzymatic inhibition assay

doi:10.1110/ps.036186.108

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	Three flavonoids targeting the beta-hydroxyacyl-acyl carrier protein dehydratase from Helicobacter pylori: Crystal structure characterization with enzymatic inhibition assay
	Zhang, Liang 2; Kong, Yunhua 2; Wu, Dalei 2; Zhang, Haitao 2; Wu, Jian 1; Chen, Jing2 ; Ding, Jianping 1; Hu, Lihong 2; Jiang, Hualiang2 ; Shen, Xu2
刊名	PROTEIN SCIENCE
	2008-11
卷号	17 期号:11 页码:1971-1978
关键词	HpFabZ quercetin apigenin (S)-sakuranetin complex structure inhibitory mechanism
ISSN号	0961-8368
DOI	10.1110/ps.036186.108
文献子类	Article
英文摘要	Flavonoids are the major functional components of many herbal and insect preparations and demonstrate varied pharmacological functions including antibacterial activity. Here by enzymatic assay and crystal structure analysis, we studied the inhibition of three flavonoids (quercetin, apigenin, and (S)-sakuranetin) against the beta-hydroxyacyl-acyl carrier protein dehydratase from Helicobacter pylori (HpFabZ). These three flavonoids are all competitive inhibitors against HpFabZ by either binding to the entrance of substrate tunnel B (binding model A) or plugging into the tunnel C near the catalytic residues (binding model B) mainly by hydrophobic interaction and hydrogen-bond pattern. Surrounded by hydrophobic residues of HpFabZ at both positions of models A and B, the methoxy group at C-7 of (S)-sakuranetin seems to play an important role for the inhibitor's binding to HpFabZ, partly responsible for the higher inhibitory activity of (S)-sakuranetin than those of quercetin and apigenin against HpFabZ (IC50 in mu M: (S)-sakuranetin, 2.0 +/- 0.1; quercetin: 39.3 +/- 2.7; apigenin, 11.0 +/- 2.5). Our work is expected to supply useful information for understanding the potential antibacterial mechanism of flavonoids.
资助项目	State Key Program of Basic Research of China[2004CB518905] ; State Key Program of Basic Research of China[2006AA09Z447] ; State Key Program of Basic Research of China[2007CB914304] ; National Natural Science Foundation of China[30525024] ; National Natural Science Foundation of China[90713046] ; National Natural Science Foundation of China[20721003] ; Shanghai Science and Technology Commission[06JC14080] ; Shanghai Science and Technology Commission[03DZ19228] ; CAS Foundation[KSCX1-YW-R-18]
WOS关键词	FABZ
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
WOS记录号	WOS:000260423400010
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272773]
专题	上海中药现代化研究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	Hu, Lihong
作者单位	1.Chinese Acad Sci, State Key Lab Mol Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China 2.Chinese Acad Sci, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Zhang, Liang,Kong, Yunhua,Wu, Dalei,et al. Three flavonoids targeting the beta-hydroxyacyl-acyl carrier protein dehydratase from Helicobacter pylori: Crystal structure characterization with enzymatic inhibition assay[J]. PROTEIN SCIENCE,2008,17(11):1971-1978.
APA	Zhang, Liang.,Kong, Yunhua.,Wu, Dalei.,Zhang, Haitao.,Wu, Jian.,...&Shen, Xu.(2008).Three flavonoids targeting the beta-hydroxyacyl-acyl carrier protein dehydratase from Helicobacter pylori: Crystal structure characterization with enzymatic inhibition assay.PROTEIN SCIENCE,17(11),1971-1978.
MLA	Zhang, Liang,et al."Three flavonoids targeting the beta-hydroxyacyl-acyl carrier protein dehydratase from Helicobacter pylori: Crystal structure characterization with enzymatic inhibition assay".PROTEIN SCIENCE 17.11(2008):1971-1978.