Quercetin binds to calcineurin at a similar region to cyclosporin A and tacrolimus

Hong Lei; Jing Luo; Li Tong; Li-Qin Peng; Yao Qi; Zhi-Guang Jia; Qun Wei

doi:10.1016/j.foodchem.2011.01.119

Quercetin binds to calcineurin at a similar region to cyclosporin A and tacrolimus

Food Chem. 2011 Aug 1;127(3):1169-74. doi: 10.1016/j.foodchem.2011.01.119. Epub 2011 Feb 1.

Authors

Hong Lei¹, Jing Luo¹, Li Tong¹, Li-Qin Peng¹, Yao Qi¹, Zhi-Guang Jia¹, Qun Wei²

Affiliations

¹ Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, 100875 Beijing, China.
² Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, 100875 Beijing, China. Electronic address: weiq@bnu.edu.cn.

PMID: 25214110
DOI: 10.1016/j.foodchem.2011.01.119

Abstract

Quercetin, the primary dietary flavonol, exerts a strong inhibitory effect on calcineurin (CN), a unique Ca(2+)/calmodulin-dependent serine/threonine protein phosphatase. Using fluorescence spectroscopy (FS) we showed quercetin strongly bound to calcineurin catalytic subunit (CNA) with a ratio of 1:1; we also showed that calcineurin regulatory subunit (CNB) weakened this binding. In addition, the secondary structure of CNA was much tighter in the presence of quercetin. An FS study with CNA truncated mutant CNAa showed that the binding area for quercetin was reduced to the catalytic domain of CNA. Furthermore, fluorescence resonance energy transfer (FRET) results and molecular docking indicated three potential binding sites for quercetin, which were located at a region between the active centre of CNA and the CNB binding domain, a similar binding area to that of cyclosporin A and tacrolimus. Interestingly, this region was also important for CN substrate recognition.

Keywords: Binding; Calcineurin; Fluorescence spectroscopy; Interaction; Molecular docking; Quercetin.