Yang Lijun, He Lian, Zhang Jing, An Shuai, Zhang Lei
College of Chemistry, Liaoning University, Shenyang, 110036, People's Republic of China.
J Biol Inorg Chem. 2015 Sep;20(6):1059-68. doi: 10.1007/s00775-015-1287-x. Epub 2015 Aug 4.
The potential impact on human exposure to aminotriazole (ATA) and heavy metal in the environment becomes a concerning issue. In the current study, a water-soluble Cu(II)-aminotriazole complex [Cu(II)-ATA] was synthesized. To explore the binding mechanism of the complex with human serum albumin (HSA), their effects on conformation and activity of HSA by multispectroscopic approach and molecular modeling were investigated. Further fluorescent tests revealed that the quenching mechanism of HSA by Cu(II)-ATA was overall static. Meanwhile, the obtained binding constant and thermodynamic parameters on complex-HSA interaction showed that the types of interaction force of Cu(II)-ATA and HSA were hydrogen bonding, van der Waals and electrostatic. The analysis of three-dimensional fluorescence, circular dichroism and Fourier transform infrared spectroscopy showed that Cu(II)-ATA induced the changes in the secondary structure of HSA. Molecular docking simulation was performed and docking model suggested that the complex docked into HSA at subdomain IIA. Furthermore, amino group and attractive electrostatic interaction of Cu(II)-ATA greatly contributed to the hydrogen bonding, van der Waals and electrostatic interaction between Cu(II)-ATA and HSA, as confirmed by experimental data.
环境中氨基三唑（ATA）和重金属对人体暴露的潜在影响成为一个令人担忧的问题。在当前研究中，合成了一种水溶性铜（II）-氨基三唑配合物[Cu（II）-ATA]。为了探究该配合物与人血清白蛋白（HSA）的结合机制，采用多光谱方法和分子模拟研究了它们对HSA构象和活性的影响。进一步的荧光测试表明，Cu（II）-ATA对HSA的猝灭机制总体上是静态的。同时，所获得的配合物与HSA相互作用的结合常数和热力学参数表明，Cu（II）-ATA与HSA的相互作用力类型为氢键、范德华力和静电作用。三维荧光、圆二色性和傅里叶变换红外光谱分析表明，Cu（II）-ATA诱导了HSA二级结构的变化。进行了分子对接模拟，对接模型表明该配合物在亚结构域IIA处与HSA对接。此外，如实验数据所证实，Cu（II）-ATA的氨基和有吸引力的静电相互作用对Cu（II）-ATA与HSA之间的氢键、范德华力和静电相互作用有很大贡献。
