Elucidation of the molecular determinants of neonicotinoid toxicity
| Project/Area Number |
16K21507
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Bioorganic chemistry
Biomolecular chemistry
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| Research Institution | Kindai University |
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Principal Investigator |
IHARA Makoto 近畿大学, 農学部, 准教授 (30466031)
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| Research Collaborator |
HIKIDA Mai
YUKUTA Yoshie
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | ネオニコチノイド / 殺虫剤 / ニコチン性アセチルコリン受容体 / アセチルコリン結合タンパク質 / イミダクロプリド / チアクロプリド / nAChR / アセチルコリン受容体 / 結晶構造解析 / 生体分子 / 生理学 / 生理活性 / 蛋白質 / 高分子構造・物性 |
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| Outline of Final Research Achievements |
Neonicotinoids are widely used for crop protection and veterinary use worldwilde. Recently the adverse effects of neonicotinoids have been focused, and some of them were banned from EU. In order to elucidate the molecular mechanism of such adverse effects of neonicotinoids, X-ray crystallography of acetylcholine binding protein, a surrogate protein of ligand binding domain of nicotinic acetylcholine receptors, has been employed and the X-ray crystal structures of AChBP-neonicotinoids complexes were solved. Using those structures, homology models were built and evaluated their interactions. These results suggested that LOOPs D, E and G cooperatively form neonicotinoid-fovored environment in insect nAChRs. Physiological evaluation confirmed that even single mutation at the Loop D, E and G strikingly weakened the neonicotinoid actions on insect nAChRs. These results suggest the adverse effects of neonicotinoids might be controlled through structure guided approaches.
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Report
(3 results)
Research Products
(8 results)
