Center for Medical and Bio-Allied Health Sciences Research, Ajman University, United Arab Emirates.
Department of Biochemistry, Aligarh Muslim University, Aligarh, India.
Int J Biol Macromol. 2023 Dec 31;253(Pt 1):126643. doi: 10.1016/j.ijbiomac.2023.126643. Epub 2023 Aug 30.
Neurodegeneration, a process of irreversible neuronal damage, is characterized by a damaged neuronal structure and function. The interplay between various proteins maintains homeostasis of essential metals in the brain, shielding neurons from degeneration; human transferrin (Htf) is essential in maintaining iron homeostasis. Any disruption in iron homeostasis results in the development of neurodegenerative diseases (NDs) and their pathology, mainly Alzheimer's disease (AD). Rutin is a known compound for its neuroprotective effects. In this work, we deciphered the binding of rutin with Htf in a bid to understand the interaction mechanism. The results of fluorescence and UV-vis spectroscopy demonstrated strong interaction between rutin and Htf. The enthalpy change (∆H°) and entropy change (∆S°) analysis demonstrated hydrophobic interactions as the prevalent forces. The binding mechanism of rutin was further assessed atomistically by molecular docking and extensive 200 ns molecular dynamic simulation (MD) studies; molecular docking showed binding of rutin within Htf's binding pocket. MD results suggested that binding of rutin to Htf does not cause significant structural switching or disruption of the protein's native packing. Overall, the study deciphers the binding of rutin with hTf, delineating the binding mechanism and providing a platform to use rutin in NDs therapeutics.
神经退行性变是一种不可逆的神经元损伤过程，其特征是神经元结构和功能受损。各种蛋白质的相互作用维持了大脑中必需金属的体内平衡，使神经元免受退化；人类转铁蛋白（Htf）对于维持铁的体内平衡至关重要。铁平衡的任何破坏都会导致神经退行性疾病（NDs）及其病理学的发展，主要是阿尔茨海默病（AD）。芦丁是一种已知的具有神经保护作用的化合物。在这项工作中，我们解析了芦丁与 Htf 的结合，以了解相互作用机制。荧光和紫外可见光谱的结果表明芦丁与 Htf 之间存在强烈的相互作用。焓变（∆H°）和熵变（∆S°）分析表明，疏水相互作用是主要的作用力。进一步通过分子对接和广泛的 200ns 分子动力学模拟（MD）研究原子水平评估了芦丁的结合机制；分子对接表明芦丁结合在 Htf 的结合口袋内。MD 结果表明，芦丁与 Htf 的结合不会导致蛋白质的结构明显切换或其天然包装的破坏。总的来说，该研究解析了芦丁与 hTf 的结合，描绘了结合机制，并为芦丁在 NDs 治疗中的应用提供了一个平台。
