环氧虫啶与人血清白蛋白的相互作用  

Interaction between cycloxaprid and human serum albumin

作　　者：刘晓娟[1] 邓培渊[1] 范春丽[1] 田云芳[1] LIU Xiaojuan;DENG Peiyuan;FAN Chunli;TIAN Yunfang(Zhengzhou Normal University,Zhengzhou Key Laboratory of Plant Landscape Diversity and Ecological Restoration,Zhengzhou 450044,China)

机构地区：[1]郑州师范学院郑州市植物景观多样性与生态修复重点实验室,郑州450044

出　　处：《农药学学报》2024年第1期160-167,共8页Chinese Journal of Pesticide Science

基　　金：河南省科技攻关重点项目(222102110281);河南省高等学校重点科研项目(21A220007)。

摘　　要：新烟碱类杀虫剂环氧虫啶对非靶标生物具有潜在危害,但对其毒理机理、其在人体内的运输机制等方面缺乏研究。本研究运用荧光光谱法、分子对接、分子动力学、结合自由能计算和丙氨酸扫描等方法,研究了环氧虫啶与人血清白蛋白(HSA)的结合模式。结果表明:1)环氧虫啶能有效猝灭HSA荧光,不同温度下环氧虫啶与HSA的结合常数在0.76×10^(5)~1.57×10^(5)L/mol之间,具有较强的结合能力;2)环氧虫啶结合在HSA的IIA疏水腔内,有1个结合位点;3)结合自由能分析和热力学参数计算显示,环氧虫啶和HSA结合的主要作用力是范德华力和氢键作用;4)分子动力学模拟结果显示,二者结合自由能为-25.90 kJ/mol,形成了相对稳定的复合物;5)丙氨酸突变扫描结果显示,氨基酸残基Gln459是环氧虫啶与HSA结合的关键氨基酸。该研究结果可为阐明环氧虫啶在人体内的毒性机理提供理论依据。Neonicotinoid insecticides cycloxaprid have potential harm to non-target organisms.However,there is a lack of research on its toxicological mechanisms,in vivo transport mechanisms,and other aspects.In this study,the binding mode of cycloxaprid with human serum albumin(HSA)was investigated using a combination of the following test methods:fluorescence quenching,molecular docking,molecular dynamics,binding free energy calculation,and alanine scanning.The results indicated that:1)Cycloxaprid can effectively quench HSA,and their binding constants range from 0.76×10^(5) L/mol to 1.57×10^(5) L/mol at different temperatures with strong binding ability.2)Cycloxaprid binds to the IIA hydrophobic cavity of HSA with one binding site.3)By combining free energy analysis and thermodynamic parameter calculation,the results showed that the main binding forces between cycloxaprid and HSA are van der Waals forces and hydrogen bonding interactions.4)By molecular dynamics simulation,the results showed that the binding free energy is‒25.90 kJ/mol,which formed a relatively stable complex. 5) The alanine mutation scan results showed that the aminoacid residue Gln459 is a key amino acid that binds to cycloxaprid and HSA. This research can provide atheoretical basis for elucidating the toxicology mechanism of epoxidizine in the human body.

关 键 词：环氧虫啶 人血清白蛋白 相互作用 荧光猝灭 分子对接 分子动力学 

分 类 号：S482.3[农业科学—农药学] S481.1[农业科学—植物保护]