Quercetin binds to calcineurin at a similar region to cyclosporin A and tacrolimus
Quercetin binds to calcineurin at a similar region to cyclosporin A and tacrolimus
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槲皮素与钙调神经磷酸酶的结合区域与环孢菌素 A 和他克莫司相似
DOI：
10.1016/j.foodchem.2011.01.119
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发表时间：
2011-08-01
期刊：
影响因子：
8.8
通讯作者：
Wei, Qun
中科院分区：
文献类型：
--
作者：
Lei, Hong;Luo, Jing;Wei, Qun
作为主要的膳食黄酮醇，栎素对钙调神经磷酸酶(CN)有很强的抑制作用，CN是一种独特的依赖于钙/钙调素的丝氨酸/苏氨酸蛋白磷酸酶。荧光光谱分析表明，槲皮素与钙调神经磷酸酶催化亚单位(CNA)以1：1的比例强烈结合，而钙调神经磷酸酶调节亚单位(CNB)则减弱了这种结合。此外，在槲皮素存在下，CNA的二级结构更加紧密。与CNA截短突变体CNAA的FS研究表明，槲皮素的结合区被减少到CNA的催化区。此外，荧光共振能量转移(FRET)和分子对接结果表明，槲皮素有三个潜在的结合部位，它们位于CNA活性中心和CNB结合域之间的区域，与环孢素A和他克莫司的结合区相似。有趣的是，这个区域对CN底物的识别也很重要。皇冠版权所有(C)2011由爱思唯尔有限公司出版。保留所有权利。
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.