Department of Biochemistry, Jawaharlal Nehru Medical College, Faculty of Medicine, Aligarh Muslim University, Aligarh 202002, Uttar Pradesh, India.
Center for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.
Int J Biol Macromol. 2024 Nov;280(Pt 2):135825. doi: 10.1016/j.ijbiomac.2024.135825. Epub 2024 Sep 21.
Fibrinogen (Fg), an essential plasma glycoprotein involved in the coagulation cascade, undergoes structural alterations upon exposure to various chemicals, impacting its functionality and contributing to pathological conditions. This research article explored the effects of 4-Chloro-o-phenylenediamine (4-Cl-o-PD), a common hair dye component (IUPAC = 1-Chloro-3,4-diaminobenzene), on human fibrinogen through comprehensive computational, biophysical, and biochemical approaches. The formation of a stable ligand-protein complex is confirmed through molecular docking and molecular dynamics simulations, revealing possible interaction having a favorable -4.8 kcal/mol binding energy. Biophysical results, including UV-vis and fluorescence spectroscopies, corroborated with the computational findings, whereas Fourier transform infrared spectroscopy (FT-IR) and circular dichroism spectroscopy (CD) provide insights into the alterations of secondary structures upon interaction with 4-Cl-o-PD. Anilinonaphthalene-sulfonic acid (ANS) fluorescence showed a partially unfolded protein, with enhanced α to β-sheet transition as evidenced by thioflavin T (ThT) spectroscopy and microscopy. Moreover, biochemical assays confirmed the formation of carbonyl compounds that may be responsible for the oxidation of methionine residues in fibrinogen. Electrophoresis and electron microscopy confirmed the formation of aggregates. Our findings elucidate the interaction pattern of 4-Cl-o-PD with Fg, leading to structural perturbation, which may have potential implications for fibrinogen misfolding or its aggregation. Protein aggregation or its misfolded products affect peripheral tissues and the central nervous system. Many chronic progressive diseases, like type II diabetes mellitus, Alzheimer's disease, Parkison's disease, and Creutzfeldt-Jakob disease are associated with intrinsically aberrant disordered proteins. Understanding these interactions may offer new perspectives on the safety and biocompatibility of dye compounds, which may contribute to developing improved strategies for acquired amyloidogenesis.
纤维蛋白原（Fg）是一种参与凝血级联反应的重要血浆糖蛋白，它在暴露于各种化学物质时会发生结构改变，从而影响其功能并导致病理状况。本研究论文通过综合计算、生物物理和生化方法探讨了常见染发剂成分 4-氯邻苯二胺（4-Cl-o-PD，IUPAC=1-氯-3,4-二氨基苯）对人纤维蛋白原的影响。分子对接和分子动力学模拟证实了稳定配体-蛋白复合物的形成，揭示了可能具有有利的-4.8 kcal/mol 结合能的相互作用。生物物理结果，包括紫外可见光谱和荧光光谱，与计算结果相吻合，而傅里叶变换红外光谱（FT-IR）和圆二色性光谱（CD）则提供了相互作用后二级结构变化的信息。苯胺萘磺酸（ANS）荧光显示部分展开的蛋白质，与 4-Cl-o-PD 相互作用时增强了α到β-折叠的转变，这可以通过硫代黄素 T（ThT）光谱和显微镜来证明。此外，生化测定证实了羰基化合物的形成，这可能是纤维蛋白原甲硫氨酸残基氧化的原因。电泳和电子显微镜证实了聚集体的形成。我们的研究结果阐明了 4-Cl-o-PD 与 Fg 的相互作用模式，导致结构扰动，这可能对纤维蛋白原错误折叠或聚集有潜在影响。蛋白质聚集或其错误折叠产物会影响周围组织和中枢神经系统。许多慢性进行性疾病，如 2 型糖尿病、阿尔茨海默病、帕金森病和克雅氏病，都与内在异常的无序蛋白有关。了解这些相互作用可能为染料化合物的安全性和生物相容性提供新的视角，并可能有助于开发获得性淀粉样变性的改进策略。
