...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Environmental Science & Technology >Assessment of Estrogenic Activity of Perfluoroalkyl Acids Based on Ligand-induced Conformation State of Human Estrogen Receptor
【24h】

Assessment of Estrogenic Activity of Perfluoroalkyl Acids Based on Ligand-induced Conformation State of Human Estrogen Receptor

机译：基于配体诱导的人类雌激素受体构象状态评估全氟烷基酸的雌激素活性

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Perfluoroalkyl acids (PFAAs) have been reported to interfere with the endocrine system in vivo by mimicking endogenous hormone activities and causing adverse effects. Some exoestrogens bind to estrogen receptor (ER) and subsequently induce an ER- mediated response. The transcriptional activity of ER is regulated by its distinct conformational states that are the results of ligand binding. In this work, a biosensor based on surface plasmon resonance (SPR) technique was developed which can discriminate between agonist and antagonist of human ERa (hERα) by monitoring the conformation state of the protein induced by ligand binding. The biosensor utilized the specific interaction between hERa and conformation-selective peptides. Six PFAAs with different chain lengths and acid groups were tested by the biosensor, and perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were found to be ER agonists. Kinetic analyses of direct interaction between PFAAs and hERa by SPR revealed that PFOS and PFOA were both weak binders of ER with K_D values of 2.19 and 107 μM respectively, whereas the other four PFAAs did not bind with ER. To understand the differences in ER binding affinity and estrogenic activity among the six PFAAs, molecular docking based on the crystal structure of hERα Iigand binding domain was performed. PFOS and PFOA were efficiently docked with hERα and formed hydrogen bonds with Arg394 in a manner similar to estradiol. Overall, the two 8-carbon PFAAs were assessed as weak agonists of hERa and are of potential concern.
机译：据报道，全氟烷基酸（PFAAs）通过模仿内源性激素活性并引起不良影响，从而在体内干扰内分泌系统。一些雌激素与雌激素受体（ER）结合，随后诱导ER介导的反应。 ER的转录活性受其独特的构象状态调节，这是配体结合的结果。在这项工作中，开发了一种基于表面等离振子共振（SPR）技术的生物传感器，该传感器可以通过监测配体结合诱导的蛋白质的构象状态来区分人ERa的激动剂和拮抗剂。该生物传感器利用了hERa和构象选择性肽之间的特异性相互作用。通过生物传感器测试了六个具有不同链长和酸基的PFAA，发现全氟辛烷磺酸盐（PFOS）和全氟辛酸（PFOA）是ER激动剂。通过SPR对PFAA和hERa之间直接相互作用的动力学分析表明，PFOS和PFOA都是ER的弱结合剂，K_D值分别为2.19和107μM，而其他四个PFAA不与ER结合。为了了解六个PFAA之间的ER结合亲和力和雌激素活性的差异，基于hERα配体结合域的晶体结构进行了分子对接。 PFOS和PFOA与hERα有效地对接，并以类似于雌二醇的方式与Arg394形成氢键。总体而言，两个8碳PFAA被评估为hERa的弱激动剂，可能引起关注。

著录项

  • 来源
    《Environmental Science & Technology》 |2013年第1期|634-641|共8页
  • 作者

    Yu Gao; Xinxin Li; Liang-Hong Guo;

  • 作者单位

    State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, P.O. Box 2871, 18 Shuangqing Road, Beijing 100085, China;

    State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, P.O. Box 2871, 18 Shuangqing Road, Beijing 100085, China;

    State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, P.O. Box 2871, 18 Shuangqing Road, Beijing 100085, China;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号