文献类型：期刊文献

英文题名：Interactions of Fipronil within Fish and Insects: Experimental and Molecular Modeling Studies

作者：Zhang, Bo[1];Zhang, Lei[1];He, Lujue[2];Yang, Xiaodong[1];Shi, Yali[1];Liao, Shaowei[1];Yang, Shan[1];Cheng, Jiagao[2];Ren, Tianrui[1]

机构：[1]Shanghai Normal Univ, Coll Life & Environm Sci, Dev Ctr Plant Germplasm Resources, Key Lab Resource Chem,Minist Educ, 100 Guilin Rd, Shanghai 200234, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai Key Lab Chem Biol, 130 Meilong Rd, Shanghai 200237, Peoples R China

年份：2018

卷号：66

期号：23

起止页码：5756

外文期刊名：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY

收录：;EI(收录号：20182505344328);WOS:【SCI-EXPANDED(收录号:WOS:000435525800004)】；

基金：We thank the National Natural Science Foundation of China (21642003, 21572059), the Innovation Program of Shanghai Municipal Education Commission (201701070002E00037), and the Shanghai Normal University scientific research project (SK201703).

语种：英文

外文关键词：fipronil; GABA receptors; affinity chromatography; fluorescence analysis; homology modeling

摘要：Fipronil is an efficient phenylpyrazole insecticide that acts on insect gamma-aminobutyric acid (GABA) receptors (GABARs) and has low toxicity to mammals but high toxicity to nontarget organisms such as fish. To develop novel efficient low toxicity insecticides, it is necessary to determine the detailed toxic mechanism at the molecular target level. In this work, methods including affinity chromatography, fluorescent-labeled binding assays, and molecular modeling were integrated to explore the binding of fipronil to GABARs in fish (Aristichthys nobilis) and insects (Musca domestica). Affinity chromatography revealed that fipronil acts on two different subunits of GABARs in fish and M. domestica. Moreover, fluorescence assays revealed that fipronil exhibits similar affinity to the two GABARs. The K-d and Binax of fipronil binding to the A. nobilis GABAR were 346 6 nmol/L and 40.6 +/- 3.5 pmol/mg of protein, respectively. And the K-d and B-max of fipronil binding to the GABAR in M. domestica brain were 109 +/- 9 nM and 21.3 +/- 2.5 pmol/mg of protein, respectively. In addition, similar fipronil binding positions but different binding modes were observed in docking studies with Brachydanio rerio var. and M. domestica GABARs. These findings indicated similar interactions of fipronil with fish and insects, leading to high toxicity. The different binding features of fipronil between the two species might be helpful for the design and development of highly selective insecticides with low toxicity to fish.