溴代阻燃剂与甲状腺素运载蛋白相互作用的非变性电喷雾质谱研究

摘要

该文采用非变性电喷雾质谱法(Native electrospray ionization mass spectrometry,ESI-MS)与分子对接模拟计算(MD)分别研究了1种溴代阻燃剂和2种羟基化代谢物,即3,5,3',5'-四溴-4,4'-二羟基基二苯砜(TBS)、4-羟基-2,2',3,4',5,5',6-八溴联苯醚(4-OH-BDE-187)、6-羟基-2,2',3,4,4',5,5'-八溴联苯醚(6-OH-BDE-180)与甲状腺素运载蛋白(TTR)的相互作用情况.ESI-MS结果表明,在37℃及生理pH值条件下的醋酸铵缓冲溶液中,TBS与TTR蛋白可形成稳定的化学计量比为1:1的复合物,4-OH-BDE-187、6-OH-BDE-180可与TTR蛋白分别形成稳定的化学计量比为1:1和2:1的复合物.通过分子对接模拟计算方法推测了上述3种配体与TTR可能的结合模型,发现3种配体与TTR的结合位点位于ASP-74残基附近.研究结果可为进一步了解溴代阻燃剂及其羟基化代谢产物体内的生物过程及毒性机制提供实验基础.%In this work,the interactions between transthyretin(TTR) and one brominated flame retardant (BFR) and two hydroxylated BFRs,namely 3,5,3',5'-tetrabromo-4,4'-dihydroxydiphenylsulfon(TBS),4-hydroxy-2,2',3,4',5,5',6-heptabromodiphenyl ether (4-OH-BDE-187) and 6-hydroxy-2,2',3,4,4',5,5'-heptabromodiphenyl ether (6-OH-BDE-180),were studied by native electrospray ionization mass spectrometry (Native ESI-MS) and molecular docking simulation (MDS).ESI-MS results indicated that,in a 37 ℃ physiological pH value buffer,TBS,4-OH-BDE-187 and 6-OH-BDE-180 could stably combine with TTR by the stoichiometric ratios of 1:1,1:1 and 2:1 to form TTR complexes,respectively.Molecular docking simulation was performed to generate the models of the protein complexes formed by these three ligands binding toTTR.MDS results demonstrated that the binding sites of TTR with these three ligands may be in the pocket around ASP 74 residue.The study is helpful for understanding the toxicology mechanisms of brominated flame retardants and their hydroxylated metabolites.