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

被引：29

作者：

Lei, Hong ^{[1
]}

Luo, Jing ^{[1
]}

Tong, Li ^{[1
]}

Peng, Li-qin ^{[1
]}

Qi, Yao ^{[1
]}

Jia, Zhi-guang ^{[1
]}

Wei, Qun ^{[1
]}

机构：

[1] Beijing Normal Univ, Dept Biochem & Mol Biol, Beijing Key Lab, Beijing 100875, Peoples R China

来源：

FOOD CHEMISTRY | 2011年 / 127卷 / 03期

基金：

美国国家科学基金会;

关键词：

Quercetin; Binding; Calcineurin; Fluorescence spectroscopy; Molecular docking; Interaction; CRYSTAL-STRUCTURE; ACTIVATION; INHIBITION; COMMON; NFAT;

D O I：

10.1016/j.foodchem.2011.01.119

中图分类号：

O69 [应用化学];

学科分类号：

070301 [无机化学];

摘要：

Quercetin, the primary dietary flavonol, exerts a strong inhibitory effect on calcineurin (CN), a unique Ca2+/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. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved.

引用

页码：1169 / 1174

页数：6

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