Characterisation of a diazinon-metabolising glutathione S-transferase in the silkworm Bombyx mori by X-ray crystallography and genome editing analysis

Kohji Yamamoto, Akifumi Higashiura, Aiko Hirowatari, Naotaka Yamada, Takuya Tsubota, Hideki Sezutsu, Atsushi Nakagawa

研究成果: ジャーナルへの寄稿記事

抄録

Previously, we found an unclassified glutathione S-transferase 2 (bmGSTu2) in the silkworm Bombyx mori that conjugates glutathione to 1-chloro-2,4-dinitrobenzene and also metabolises diazinon, an organophosphate insecticide. Here, we provide a structural and genome-editing characterisation of the diazinon-metabolising glutathione S-transferase in B. mori. The structure of bmGSTu2 was determined at 1.68 Å by X-ray crystallography. Mutation of putative amino acid residues in the substrate-binding site showed that Pro13, Tyr107, Ile118, Phe119, and Phe211 are crucial for enzymatic function. bmGSTu2 gene disruption resulted in a decrease in median lethal dose values to an organophosphate insecticide and a decrease in acetylcholine levels in silkworms. Taken together, these results indicate that bmGSTu2 could metabolise an organophosphate insecticide. Thus, this study provides insights into the physiological role of bmGSTu2 in silkworms, detoxification of organophosphate insecticides, and drug targets for the development of a novel insecticide.

元の言語英語
記事番号16835
ジャーナルScientific reports
8
発行部数1
DOI
出版物ステータス出版済み - 12 1 2018

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Diazinon
Bombyx
X Ray Crystallography
Insecticides
Glutathione Transferase
Organophosphates
Morus
Acetylcholine
Binding Sites
Gene Editing
Amino Acids
Mutation
Pharmaceutical Preparations
Genes

All Science Journal Classification (ASJC) codes

  • General

これを引用

Characterisation of a diazinon-metabolising glutathione S-transferase in the silkworm Bombyx mori by X-ray crystallography and genome editing analysis. / Yamamoto, Kohji; Higashiura, Akifumi; Hirowatari, Aiko; Yamada, Naotaka; Tsubota, Takuya; Sezutsu, Hideki; Nakagawa, Atsushi.

:: Scientific reports, 巻 8, 番号 1, 16835, 01.12.2018.

研究成果: ジャーナルへの寄稿記事

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