梁峰;穆云松;李会仙;冯承莲;

• 1:河南城建学院市政与环境工程学院
• 2:中国环境科学研究院环境基准与风险评估国家重点实验室

摘要(Abstract)：

近年来,羟基多溴代二苯醚(OH-PBDEs)的类甲状腺素效应逐渐引起人们的关注,然而其结构效应关系和致毒机制尚不清楚。甲状腺激素结合球蛋白(TBG)和运甲状腺素蛋白(TTR)是人体转运甲状腺素的重要蛋白,通过计算毒理学手段可以揭示OH-PBDEs的微观毒理机制。利用分子对接技术研究OH-PBDEs与TBG、TTR的结合模式和构象特征,识别关键氢键氨基酸为赖氨酸Lys270(TBG),亮氨酸Leu110(TTR)和丝氨酸Ser117(TTR)。基于活性构象特征,构建14种典型OH-PBDEs的3D-QSAR模型,定量预测OH-PBDEs与TBG、TTR的结合亲和力。最佳预测模型的相关系数r2分别为0.966(TBG)和0.961(TTR),抽一法交叉验证相关系数q2分别为0.560(TBG)和0.525(TTR)。研究发现,OH-PBDEs的静电和氢键作用可增强结合亲和力,分别贡献65.4%(TBG)和68.7%(TTR)。研究结果为揭示OH-PBDEs与甲状腺素转运蛋白的相互作用提供新视角,有助于全面评价OH-PBDEs对人体甲状腺素调节功能的损伤。

关键词(KeyWords)： 羟基多溴代二苯醚;甲状腺素结合球蛋白;运甲状腺素蛋白;竞争抑制;比较分子场分析;比较相似性指数分析

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金面上项目(41673087);; 河南省科技攻关计划项目(162102310389);; 河南省教育厅科学技术研究重点项目(14A610012)

作者(Author): 梁峰;穆云松;李会仙;冯承莲;

Email:

DOI:

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