title: Quercetin binds to calcineurin at a similar region to cyclosporin A and tacrolimus.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, 100875 Beijing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Lei
authors.affiliation: Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, 100875 Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, 100875 Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Tong
authors.affiliation: Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, 100875 Beijing, China.
authors.forename: Li-Qin
authors.initials: LQ
authors.lastname: Peng
authors.affiliation: Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, 100875 Beijing, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, 100875 Beijing, China.
authors.forename: Zhi-Guang
authors.initials: ZG
authors.lastname: Jia
authors.affiliation: Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, 100875 Beijing, China. Electronic address: weiq@bnu.edu.cn.
authors.forename: Qun
authors.initials: Q
authors.lastname: Wei
keywords: Binding; Calcineurin; Fluorescence spectroscopy; Interaction; Molecular docking; Quercetin