School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
College of Chemistry, Green Catalysis center, Henan Joint International Research Laboratory of Green Construction of Functional Molecules and their Bioanalytical Applications, Zhengzhou University, Zhengzhou, China.
J Mol Recognit. 2021 Jun;34(6):e2889. doi: 10.1002/jmr.2889. Epub 2021 Mar 1.
In this paper, the effects of three isoflavones including daidzein, genistein, and puerarin on fibrillation of hen egg-white lysozyme were investigated by various analytical methods. The results demonstrated that all isoflavones could effectively inhibit the fibrillogenesis of hen egg-white lysozyme and destabilized the preformed fibrils of hen egg-white lysozyme in a dose-dependent manner. To further understand the inhibition mechanism, molecular modeling was carried out. The docking results demonstrated that the isoflavones could bind to two key fibrogenic sites in hen egg-white lysozyme through van der Waals force, electrostatic forces, and hydrogen bonding, as well as σ-π stacking. By these means, isoflavones could not only obviously enhance the hydrophobicity of the binding sites, but also greatly stabilize the native state of HEWL, which was able to postpone the fibrosis process of hen egg-white lysozyme.
本文采用多种分析方法研究了三种异黄酮（大豆苷元、染料木黄酮和葛根素）对鸡卵清白溶菌酶纤维形成的影响。结果表明，所有异黄酮均可有效抑制鸡卵清白溶菌酶的纤维形成，并以剂量依赖的方式使鸡卵清白溶菌酶原纤维不稳定。为了进一步了解抑制机制，进行了分子建模。对接结果表明，异黄酮可通过范德华力、静电力和氢键以及σ-π堆积与鸡卵清白溶菌酶的两个关键成纤维部位结合。通过这些方式，异黄酮不仅可以明显增强结合部位的疏水性，还可以极大地稳定 HEWL 的天然状态，从而延缓鸡卵清白溶菌酶的纤维化过程。
