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, Atushi

doi:https://doi.org/10.1038/s41598-018-35207-8

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 et al.

Scientific Reports, 2018, 8, 35207

Number of Access:786（2025-08-13 23:54 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/73669

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Title	Characterisation of a diazinon-metabolising glutathione S-transferase in the silkworm Bombyx mori by X-ray crystallography and genome editing analysis
Creator	NRID 1000000346834 1000000346834 CreatorName Yamamoto, Kohji
	NRID 1000090598129 1000090598129 CreatorName Higashiura, Akifumi
	CreatorName Hirowatari, Aiko
	NRID 1000020304769 1000020304769 CreatorName Yamada, Naotaka
	NRID 1000000612772 1000000612772 CreatorName Tsubota, Takuya
	NRID 1000070342805 1000070342805 CreatorName Sezutsu, Hideki
	NRID 1000020188890 1000020188890 ORCID 0000-0002-1700-7861 0000-0002-1700-7861 researchmap permalink atsushi_nakagawa atsushi_nakagawa Scopus Author ID 7202934909 7202934909 CreatorName Nakagawa, Atushi
Description	Yamamoto, K., Higashiura, A., Hirowatari, A. et al. Characterisation of a diazinon-metabolising glutathione S-transferase in the silkworm Bombyx mori by X-ray crystallography and genome editing analysis. Sci Rep 8, 16835 (2018) doi:10.1038/s41598-018-35207-8
Abstract	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.
Publisher	Springer Nature
Source Title	Scientific Reports
Volume (Issue)	8
Page	35207
Date of Issued	2018-11
Language	English
Handle URL	https://hdl.handle.net/11094/73669
eISSN	20452322
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1038/s41598-018-35207-8
Relation.isIdenticalTo	PMID 30443011
Access Rights	open access
CopyRight	© 2018 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Scientific Reports. 2018, 8, p. 35207
DC.title	Characterisation of a diazinon-metabolising glutathione S-transferase in the silkworm Bombyx mori by X-ray crystallography and genome editing analysis
DC.creator	Yamamoto, Kohji
	Higashiura, Akifumi
	Hirowatari, Aiko
	Yamada, Naotaka
	Tsubota, Takuya
	Sezutsu, Hideki
	Nakagawa, Atushi
DC.publisher	Springer Nature
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2018-11
DC.identifier	https://doi.org/10.1038/s41598-018-35207-8
DC.description	Yamamoto, K., Higashiura, A., Hirowatari, A. et al. Characterisation of a diazinon-metabolising glutathione S-transferase in the silkworm Bombyx mori by X-ray crystallography and genome editing analysis. Sci Rep 8, 16835 (2018) doi:10.1038/s41598-018-35207-8
DCTERMS.abstract	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.
DC.rights	© 2018 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	73669
citation_title	Characterisation of a diazinon-metabolising glutathione S-transferase in the silkworm Bombyx mori by X-ray crystallography and genome editing analysis
citation_author	Yamamoto, Kohji
	Higashiura, Akifumi
	Hirowatari, Aiko
	Yamada, Naotaka
	Tsubota, Takuya
	Sezutsu, Hideki
	Nakagawa, Atushi
citation_publisher	Springer Nature
citation_language	English
citation_date	2018-11
citation_journal_title	Scientific Reports
citation_volume	8
citation_firstpage	35207
citation_doi	https://doi.org/10.1038/s41598-018-35207-8
citation_pmid	30443011
citation_public_url	https://hdl.handle.net/11094/73669

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

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