Structure-based investigation on the binding interaction of hydroxylated polybrominated diphenyl ethers with thyroxine transport proteins
文献类型：期刊论文
| 作者 | Cao, Jie ; Lin, Yuan ; Guo, Liang-Hong ; Zhang, Ai-Qian ; Wei, Yin ; Yang, Yu |
| 刊名 | TOXICOLOGY
 |
| 出版日期 | 2010-11-09 |
| 卷号 | 277期号:3页码:20-28 |
| 关键词 | Hydroxylated polybrominated diphenyl ether Thyroid hormone transport protein Fluorescence Circular dichroism Molecular docking |
| 中文摘要 | Polybrominated diphenyl ethers (PBDEs) have been shown to alter thyroid hormone level in experimental animals. One of the possible mechanisms for hormone disruption is the competitive binding of hydroxylated PBDEs (OH-PBDEs) with hormone transport proteins. In this study, binding interaction of 14 diversely structured OH-PBDEs with two thyroxine transport proteins was investigated by fluorescence displacement assay, circular dichroism, and molecular docking. Binding affinity of the 14 OH-PBDEs with transthyretin (TTR) and thyroxine-binding globulin (TBG) was measured by competitive fluorescence displacement assay. The binding constant was found to fall in the range of 1.4 x 10(7) M(-1) and 6.9 x 10(8) M(-1) for TTR, and between 6.5 x 10(6) M(-1) and 2.2 x 10(8) M(-1) for TBG. Binding affinity increased significantly with bromination number from 1 to 4, whereas 5- and 6-brominated diphenyl ethers did not show any further increase. Protein secondary structural change of TTR and TBG upon binding with 5-OH-BDE-047 was investigated by circular dichroism. The spectral change displayed a pattern similar to the one with thyroxine, suggesting that the environmental chemical binds to the two proteins at the same sites as the hormone. In molecular docking analysis, a ligand-binding channel in TTR was revealed for OH-PBDEs binding, which appeared to be mostly hydrophobic inside but guarded by positively charged residue Lysl 5 at the entrance. Binding affinity of the 14 OH-PBDEs with TTR could be rationalized reasonably well by their pocket binding mode and hydrophobic characteristics. Based on the binding constant obtained in this work, possibility of in vitro competitive displacement of thyroid hormones from the transport proteins by OH-PBDEs was evaluated. (C) 2010 Elsevier Ireland Ltd. All rights reserved. |
| WOS记录号 | WOS:000284436000004 |
| 源URL | [http://ir.rcees.ac.cn/handle/311016/21149]  |
| 专题 | 生态环境研究中心_环境化学与生态毒理学国家重点实验室 |
| 推荐引用方式 GB/T 7714 | Cao, Jie,Lin, Yuan,Guo, Liang-Hong,et al. Structure-based investigation on the binding interaction of hydroxylated polybrominated diphenyl ethers with thyroxine transport proteins[J]. TOXICOLOGY,2010,277(3):20-28. |
| APA | Cao, Jie,Lin, Yuan,Guo, Liang-Hong,Zhang, Ai-Qian,Wei, Yin,&Yang, Yu.(2010).Structure-based investigation on the binding interaction of hydroxylated polybrominated diphenyl ethers with thyroxine transport proteins.TOXICOLOGY,277(3),20-28. |
| MLA | Cao, Jie,et al."Structure-based investigation on the binding interaction of hydroxylated polybrominated diphenyl ethers with thyroxine transport proteins".TOXICOLOGY 277.3(2010):20-28. |
入库方式： OAI收割
来源：生态环境研究中心
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