D-Alanine: D-alanine ligase as a new target for the flavonoids quercetin and apigenin

doi:10.1016/j.ijantimicag.2008.06.010

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	D-Alanine: D-alanine ligase as a new target for the flavonoids quercetin and apigenin
	Wu, Dalei; Kong, Yunhua; Chen, Cong Han Jing; Hu, Lihong; Jiang, Hualiang; Shen, Xu
刊名	INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
	2008-11
卷号	32 期号:5 页码:421-426
关键词	Flavonoids Quercetin Apigenin D-Alanine:D-alanine ligase D-Cycloserine MIC
ISSN号	0924-8579
DOI	10.1016/j.ijantimicag.2008.06.010
文献子类	Article
英文摘要	Flavonoids are polyphenolic compounds that are ubiquitous in nature. They possess varied promising properties for medical use. Quercetin (3,3',4',5,7-pentahydroxyflavone) and apigenin (4',5,7-trihydroxyflavone) are two representative flavonoids, both of which have been reported to possess antibacterial activity by acting on multiple targets. Here, we determined that D-alanine: D-alanine ligase (Ddl) is another new target for quercetin and apigenin. Kinetic analysis indicated that these two flavonoids function as reversible inhibitors that are competitive with the substrate ATP of Ddl, whereas they are non-competitive with the other substrate D-Ala. The fact that quercetin showed lower 50% inhibitory concentration (IC50) and inhibitor binding constant (K-i) values than apigenin against both the Helicobacter pylori Ddl and the Escherichia coli DdlB implies that the two additional hydroxyls on the flavone skeleton of quercetin in structure might facilitate its inhibitory activity and binding affinity to Ddl. This work is expected to help shed more light on the potential antibacterial mechanism of flavonoids. (C) 2008 Elsevier B. V. and the International Society of Chemotherapy. All rights reserved.
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	ALANYL-D-ALANINE ; HELICOBACTER-PYLORI ; D-CYCLOSERINE ; DNA GYRASE ; INHIBITION ; ENZYMES ; BIOSYNTHESIS ; MECHANISMS ; FABZ
WOS研究方向	Infectious Diseases ; Microbiology ; Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER SCIENCE BV
WOS记录号	WOS:000261995800011
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279453]
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	Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Wu, Dalei,Kong, Yunhua,Chen, Cong Han Jing,et al. D-Alanine: D-alanine ligase as a new target for the flavonoids quercetin and apigenin[J]. INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS,2008,32(5):421-426.
APA	Wu, Dalei,Kong, Yunhua,Chen, Cong Han Jing,Hu, Lihong,Jiang, Hualiang,&Shen, Xu.(2008).D-Alanine: D-alanine ligase as a new target for the flavonoids quercetin and apigenin.INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS,32(5),421-426.
MLA	Wu, Dalei,et al."D-Alanine: D-alanine ligase as a new target for the flavonoids quercetin and apigenin".INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS 32.5(2008):421-426.