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Article

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

1
Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center of Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071, China
2
Graduate University of Chinese Academy of Science, Beijing 100049, China
3
Laboratory of Computer-Aided Drug Design and Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China
*
Authors to whom correspondence should be addressed.
Received: 2 February 2019 / Revised: 21 February 2019 / Accepted: 4 March 2019 / Published: 7 March 2019
(This article belongs to the Special Issue Chemical Biology of Antimicrobial Resistance)
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 π-π 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. View Full-Text
Keywords: two-component system; histidine kinase; luteolin; ATP; NMR; molecular docking; inhibition two-component system; histidine kinase; luteolin; ATP; NMR; molecular docking; inhibition
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MDPI and ACS Style

Zhou, Y.; Huang, L.; Ji, S.; Hou, S.; Luo, L.; Li, C.; Liu, M.; Liu, Y.; Jiang, L. Structural Basis for the Inhibition of the Autophosphorylation Activity of HK853 by Luteolin. Molecules 2019, 24, 933. https://0-doi-org.brum.beds.ac.uk/10.3390/molecules24050933

AMA Style

Zhou Y, Huang L, Ji S, Hou S, Luo L, Li C, Liu M, Liu Y, Jiang L. Structural Basis for the Inhibition of the Autophosphorylation Activity of HK853 by Luteolin. Molecules. 2019; 24(5):933. https://0-doi-org.brum.beds.ac.uk/10.3390/molecules24050933

Chicago/Turabian Style

Zhou, Yuan, Liqun Huang, Shixia Ji, Shi Hou, Liang Luo, Conggang Li, Maili Liu, Yixiang Liu, and Ling Jiang. 2019. "Structural Basis for the Inhibition of the Autophosphorylation Activity of HK853 by Luteolin" Molecules 24, no. 5: 933. https://0-doi-org.brum.beds.ac.uk/10.3390/molecules24050933

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