Interaction of perfluoroalkyl acids with human liver fatty acid-binding protein
文献类型：期刊论文
| 作者 | Sheng, Nan; Li, Juan; Liu, Hui; Zhang, Aiqian; Dai, Jiayin |
| 刊名 | ARCHIVES OF TOXICOLOGY
 |
| 出版日期 | 2016-01 |
| 卷号 | 90期号:1页码:217-227 |
| 关键词 | Perfluorinated compounds Human liver fatty acid-binding protein Interaction Isothermal titration calorimetry Molecular simulation |
| 英文摘要 | Perfluoroalkyl acids (PFAAs) are highly persistent and bioaccumulative, resulting in their broad distribution in humans and the environment. The liver is an important target for PFAAs, but the mechanisms behind PFAAs interaction with hepatocyte proteins remain poorly understood. We characterized the binding of PFAAs to human liver fatty acid-binding protein (hL-FABP) and identified critical structural features in their interaction. The binding interaction of PFAAs with hL-FABP was determined by fluorescence displacement and isothermal titration calorimetry (ITC) assay. Molecular simulation was conducted to define interactions at the binding sites. ITC measurement revealed that PFOA/PFNA displayed a moderate affinity for hL-FABP at a 1: 1 molar ratio, a weak binding affinity for PFHxS and no binding for PFHxA. Moreover, the interaction was mainly mediated by electrostatic attraction and hydrogen bonding. Substitution of Asn111 with Asp caused loss of binding affinity to PFAA, indicating its crucial role for the initial PFAA binding to the outer binding site. Substitution of Arg122 with Gly caused only one molecule of PFAA to bind to hL-FABP. Molecular simulation showed that substitution of Arg122 increased the volume of the outer binding pocket, making it impossible to form intensive hydrophobic stacking and hydrogen bonds with PFOA, and highlighting its crucial role in the binding process. The binding affinity of PFAAs increased significantly with their carbon number. Arg122 and Asn111 played a pivotal role in these interactions. Our findings may help understand the distribution pattern, bioaccumulation, elimination, and toxicity of PFAAs in humans. |
| 收录类别 | SCI |
| 源URL | [http://ir.rcees.ac.cn/handle/311016/35879]  |
| 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 | Sheng, Nan,Li, Juan,Liu, Hui,et al. Interaction of perfluoroalkyl acids with human liver fatty acid-binding protein[J]. ARCHIVES OF TOXICOLOGY,2016,90(1):217-227. |
| APA | Sheng, Nan,Li, Juan,Liu, Hui,Zhang, Aiqian,&Dai, Jiayin.(2016).Interaction of perfluoroalkyl acids with human liver fatty acid-binding protein.ARCHIVES OF TOXICOLOGY,90(1),217-227. |
| MLA | Sheng, Nan,et al."Interaction of perfluoroalkyl acids with human liver fatty acid-binding protein".ARCHIVES OF TOXICOLOGY 90.1(2016):217-227. |
入库方式： OAI收割
来源：生态环境研究中心
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