Inhibitory effects of the dietary flavonoid quercetin on the enzyme activity of zinc(II)-dependent yeast alcohol dehydrogenase: Spectroscopic and molecular docking studies
Inhibitory effects of the dietary flavonoid quercetin on the enzyme activity of zinc(II)-dependent yeast alcohol dehydrogenase: Spectroscopic and molecular docking studies
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DOI：
10.1016/j.ijbiomac.2016.11.047
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发表时间：
2017-02-01
影响因子：
8.2
通讯作者：
Das, Suman
中科院分区：
文献类型：
--
作者：
Bhuiya, Sutanwi;Hague, Lucy;Das, Suman
采用多光谱技术研究了酵母金属酶乙醇脱氢酶（ADH）与槲皮素（QTN）的相互作用。在这里，我们的特点是QTN和Zn 2+在水溶液中的复合物之间的形成，然后检查这种复合物形成的影响上的酶活性的锌（II）依赖性酶醇脱氢酶从酵母。我们已经观察到在QTN存在下ADH的酶活性的抑制。酶抑制动力学实验表明，QTN是酵母ADH的非竞争性抑制剂。在QTN存在下，ADH的圆二色性（CD）光谱的扰动观察到由于ADH与上述黄酮络合的结构变化。我们的研究结果表明，ADH的构象变化，由于去除Zn 2+存在于酶的QTN。这是进一步建立了分子模拟研究表明，类黄酮结合的锌离子，保持了三级结构的金属酶。因此，QTN仅提取酶中存在的一半Zn 2+离子，即每个单体一个Zn 2+离子。从目前的研究中，ADH的结构改变和酶活性的损失归因于QTN和Zn ~（2+）之间的络合物的形成。(C)2016爱思唯尔B. V.保留所有权利。
A multispectroscopic exploration was employed to investigate the interaction between the metalloenzyme alcohol dehydrogenase (ADH) from yeast with bioflavonoid quercetin (QTN). Here, we have characterized the complex formation between QTN and Zn2+ in aqueous solution and then examined the effect of such complex formation on the enzymatic activity of a zinc(II)-dependent enzyme alcohol dehydrogenase from yeast. We have observed an inhibition of enzymatic activity of ADH in presence of QTN. Enzyme inhibition kinetic experiments revealed QTN as a non-competitive inhibitor of yeast ADH. Perturbation of Circular dichroic (CD) spectrum of ADH in presence of QTN is observed due to the structural changes of ADH on complexation with the above flavonoid. Our results indicate a conformational change of ADH due to removal of Zn2+ present in the enzyme by QTN. This was further established by molecular modeling study which shows that the flavonoid binds to the Zn2+ ion which maintains the tertiary structure of the metallo-enzyme. So, QTN abstracts only half of the Zn2+ ions present in the enzyme i.e. one Zn2+ ion per monomer. From the present study, the structural alteration and loss of enzymatic activity of ADH are attributed to the complex formation between QTN and Zn2+. (C) 2016 Elsevier B.V. All rights reserved.