Kour Harman Deep, Pathania Apoorva, Pathania Anu Radha
Department of Chemistry, University Institute of Sciences, Chandigarh University, Mohali, Punjab, India.
Curr Protein Pept Sci. 2025;26(3):213-225. doi: 10.2174/0113892037318575240919054053.
Metadoxine, also known as pyruvate dehydrogenase activator, is a small molecule drug that has been used in the treatment of various medical conditions. Bovine serum albumin is a commonly studied protein that serves as a plasmatic for understanding protein-drug interactions due to its abundance.
This research suggests that metadoxine can bind to bovine serum albumin with moderate affinity, leading to an alteration in the secondary structure of the protein, which may also influence the protein's stability and function, which could provide a comprehensive understanding of the interaction at a molecular level. In this study, a variety of methodologies wereused to determine various thermodynamic parameters.
The study uses UV-visible, Fluorescence, Fourier-transform infrared, Circular dichroism spectroscopy, and Molecular docking to analyze the interaction between bovine serum albumin and metadoxine, providing thermodynamic parameters for understanding the protein structure and its binding.
The binding of metadoxine with bovine serum albumin, causes a hyperchromic shift. In fluorescence spectroscopy, the value of the Stern Volmer increases constantly with an increase in temperature, suggesting a stronger interaction between the Metadoxine and the Bovine serum albumin, leading to dynamic quenching. Additionally, Fourier-transform infrared and circular dichroism indicated a reduction in the secondary structure of Bovine serum albumin.
The interactions between metadoxine and bovine serum albumin, cause hyperchromic shift revealed by UV-visible spectroscopy, whereas in Fluorescence spectroscopy, the value of the Stern Volmer constant increases with an increase in temperature, suggesting a stronger interaction between the MD and the BSA, leading to dynamic quenching. Additionally, Fourier-transform infrared and circular dichroism spectroscopy indicated a reduction in the secondary structure of the protein, as evidenced by the shifting of the amide II band and leading to a slight decrease in the α- helix content. The molecular docking shows that metadoxine was docked in the subdomain IIA binding pocket of BSA.
美他多辛，也被称为丙酮酸脱氢酶激活剂，是一种已用于治疗多种病症的小分子药物。牛血清白蛋白是一种常被研究的蛋白质，因其含量丰富，可作为研究蛋白质 - 药物相互作用的血浆模型。
本研究表明美他多辛能以中等亲和力与牛血清白蛋白结合，导致蛋白质二级结构改变，这也可能影响蛋白质的稳定性和功能，从而在分子水平上全面理解这种相互作用。在本研究中，使用了多种方法来测定各种热力学参数。
该研究采用紫外可见光谱、荧光光谱、傅里叶变换红外光谱、圆二色光谱和分子对接技术来分析牛血清白蛋白与美他多辛之间的相互作用，为理解蛋白质结构及其结合提供热力学参数。
美他多辛与牛血清白蛋白的结合导致增色效应。在荧光光谱中，斯特恩 - 沃尔默值随温度升高而持续增加，表明美他多辛与牛血清白蛋白之间的相互作用更强，导致动态猝灭。此外，傅里叶变换红外光谱和圆二色光谱表明牛血清白蛋白的二级结构减少。
美他多辛与牛血清白蛋白之间的相互作用导致紫外可见光谱显示增色效应，而在荧光光谱中，斯特恩 - 沃尔默常数的值随温度升高而增加，表明美他多辛与牛血清白蛋白之间的相互作用更强，导致动态猝灭。此外，傅里叶变换红外光谱和圆二色光谱表明蛋白质的二级结构减少，酰胺 II 带的位移证明了这一点，并导致α - 螺旋含量略有下降。分子对接显示美他多辛对接在牛血清白蛋白的亚结构域 IIA 结合口袋中。
