噻螨酮与人血清白蛋白的作用机制

Studies on the interaction mechanism for human serum albumin with hexythiazox

用分子对接方法及紫外-可见吸收光谱、同步荧光光谱、三维荧光光谱等实验手段研究了噻螨酮(HEX)与人血清白蛋白(HSA)的相互作用及对HSA构象的影响.预测结果表明,HEX能与HSA发生相互作用,且作用位点site II比site I的打分小约4.5.实验结果表明,HEX猝灭HSA的内源荧光且作用机制为静态猝灭;HEX使HSA周围的微环境发生变化,导致蛋白质的肽链结构改变;298和291 K时HEX与HSA相互作用的结合常数(KA)和结合位点数分别为7.35×103 mol/L、0.82和1.02×104 mol/L、0.86,证实HEX仅在site II存在作用位点;HEX与Trp214的结合距离为3.01 nm,作用力主要为氢键、范德华力和疏水作用力.这些研究所获得的多种信息有助于在分子水平上理解农药对人体造成的毒性及可能的生物累积性.

The interaction of human serum albumin （HSA） with hexythiazox （HEX） and the alterations of protein secondary structure in the presence of HEX were investigated by molecular docking, UV-vis absorption spectrometry, synchronous fluorescence spectrometry and three-dimensional fluorescence spectroscopy. Forecasting molecular docking results revealed that HEX could bind on site I and site II where it was easier to combine in HSA. The experiment results indicated that HEX had a strong ability to quench the intrinsic fluorescence of HSA through static quenching procedure. At the same time, HEX altered HSA surrounding microenvironment and led to change in the peptide chain structure of the protein. Binding affinity （KA） and the amounts of binding sites （n） between HEX and HSA at 298 and 291 K were estimated as 7.35 x 10^3 tool/L, 0.82 and 1.02 x 10^4 mol/L, 0.86, respectively, which confirmed that HEX could only bind on site II. The binding power between HEX and HSA involved mainly hydrogen bonds, van der Waals and hydrophobic forces, and an apparent distance between the Trp214 and HEX was 3.01 nm. The various informations of these studies help to understand toxicity of pesticide to humans and their bioaccumulative potential at the molecular level.