Structural Basis for the Inhibition of the Autophosphorylation Activity of HK853 by Luteolin

doi:10.3390/molecules24050933

	Structural Basis for the Inhibition of the Autophosphorylation Activity of HK853 by Luteolin
	Jiang, Ling 3; Liu, Yixiang 3; Liu, Maili 3; Li, Conggang 3; Luo, Liang 2,3; Hou, Shi 1; Ji, Shixia 2,3; Huang, Liqun 2,3; Zhou, Yuan 2,3
刊名	MOLECULES
	2019-03-01
卷号	24 期号:5 页码:11
关键词	two-component system histidine kinase luteolin ATP NMR molecular docking inhibition
ISSN号	1420-3049
DOI	10.3390/molecules24050933
英文摘要	The two-component system (TCS) is a significant signal transduction system for bacteria to adapt to complicated and variable environments, and thus has recently been regarded as a novel target for developing antibacterial agents. The natural product luteolin (Lut) can inhibit the autophosphorylation activity of the typical histidine kinase (HK) HK853 from Thermotoga maritime, but the inhibition mechanism is not known. Herein, we report on the binding mechanism of a typical flavone with HK853 by using solution NMR spectroscopy, isothermal titration calorimetry (ITC), and molecular docking. We show that luteolin inhibits the activity of HK853 by occupying the binding pocket of adenosine diphosphate (ADP) through hydrogen bonds and pi-pi stacking interaction structurally. Our results reveal a detailed mechanism for the inhibition of flavones and observe the conformational and dynamics changes of HK. These results should provide a feasible approach for antibacterial agent design from the view of the histidine kinases.
资助项目	National Key R&D Program of China[2017YFA0505400] ; National Science Foundation of China[21573280] ; National Science Foundation of China[21603268] ; National Science Foundation of China[21735007]
WOS关键词	BACTERIAL HISTIDINE KINASES ; SIGNAL-TRANSDUCTION ; 2-COMPONENT ; MECHANISMS ; BINDING ; ASPARTATE
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
语种	英语
出版者	MDPI
WOS记录号	WOS:000462662900109
资助机构	National Key R&D Program of China ; National Key R&D Program of China ; National Science Foundation of China ; National Science Foundation of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Science Foundation of China ; National Science Foundation of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Science Foundation of China ; National Science Foundation of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Science Foundation of China ; National Science Foundation of China
内容类型	期刊论文
源URL	[http://ir.wipm.ac.cn/handle/112942/13756]
专题	中国科学院武汉物理与数学研究所
通讯作者	Jiang, Ling; Liu, Yixiang
作者单位	1.Beijing Inst Pharmacol & Toxicol, Lab Comp Aided Drug Design & Discovery, Beijing 100850, Peoples R China 2.Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China 3.Chinese Acad Sci, State Key Lab Magnet Resonance & Atom & Mol Phys, Natl Ctr Magnet Resonance Wuhan, Wuhan Inst Phys & Math,Key Lab Magnet Resonance B, Wuhan 430071, Hubei, Peoples R China
推荐引用方式 GB/T 7714	Jiang, Ling,Liu, Yixiang,Liu, Maili,et al. Structural Basis for the Inhibition of the Autophosphorylation Activity of HK853 by Luteolin[J]. MOLECULES,2019,24(5):11.
APA	Jiang, Ling.,Liu, Yixiang.,Liu, Maili.,Li, Conggang.,Luo, Liang.,...&Zhou, Yuan.(2019).Structural Basis for the Inhibition of the Autophosphorylation Activity of HK853 by Luteolin.MOLECULES,24(5),11.
MLA	Jiang, Ling,et al."Structural Basis for the Inhibition of the Autophosphorylation Activity of HK853 by Luteolin".MOLECULES 24.5(2019):11.