Crystal structure of aminomethyltransferase in complex with dihydrolipoyl-H-protein of the glycine cleavage system : Implications for recognition of lipoyl protein substrate, disease-related mutations, and reaction mechanism

Okamura, Kazuko; Hosaka, Harumi; Maita, Nobuo; Fujiwara, Kazuko; Yoshizawa, Akiyasu C.; Nakagawa, Atushi; Taniguchi, Hisaaki

doi:https://doi.org/10.1074/jbc.M110.110718

Crystal structure of aminomethyltransferase in complex with dihydrolipoyl-H-protein of the glycine cleavage system : Implications for recognition of lipoyl protein substrate, disease-related mutations, and reaction mechanism

Okamura, Kazuko; Hosaka, Harumi; Maita, Nobuo et al.

Journal of Biological Chemistry, 2010, 285(24), 18684-18692

Number of Access:736（2025-08-15 06:45 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/73655

Link to primary information

File	Format	Terms of use	Size	Views	Date.Available	Description	information
JBC285_24_18684	pdf	None	2.68 MB	183	2019.12.09

Item Information

Output File Export EndNote Basic Export Mendeley

Title	Crystal structure of aminomethyltransferase in complex with dihydrolipoyl-H-protein of the glycine cleavage system : Implications for recognition of lipoyl protein substrate, disease-related mutations, and reaction mechanism
Creator	NRID 1000010108863 1000010108863 CreatorName Okamura, Kazuko Creator.Alternative Ikeda, Kazuko
	CreatorName Hosaka, Harumi
	NRID 1000000404046 1000000404046 CreatorName Maita, Nobuo
	NRID 1000020108880 1000020108880 CreatorName Fujiwara, Kazuko
	NRID 1000070551159 1000070551159 CreatorName Yoshizawa, Akiyasu C.
	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
	NRID 1000010257636 1000010257636 CreatorName Taniguchi, Hisaaki
Description	This research was originally published in Journal of Biological Chemistry. Kazuko Okamura-Ikeda, Harumi Hosaka, Nobuo Maita, Kazuko Fujiwara, Akiyasu C. Yoshizawa, Atsushi Nakagawa and Hisaaki Taniguchi. Crystal structure of aminomethyltransferase in complex with dihydrolipoyl-H-protein of the glycine cleavage system : Implications for recognition of lipoyl protein substrate, disease-related mutations, and reaction mechanism. Journal of Biological Chemistry. 2010; 285, 18684-18692. © the American Society for Biochemistry and Molecular Biology.
Abstract	Aminomethyltransferase, a component of the glycine cleavage system termed T-protein, reversibly catalyzes the degradation of the aminomethyl moiety of glycine attached to the lipoate cofactor of H-protein, resulting in the production of ammonia, 5,10-methylenetetrahydrofolate, and dihydrolipoate- bearing H-protein in the presence of tetrahydrofolate. Several mutations in the human T-protein gene are known to cause nonketotic hyperglycinemia. Here, we report the crystal structure of Escherichia coli T-protein in complex with dihydrolipoate-bearing H-protein and 5-methyltetrahydrofolate, a complex mimicking the ternary complex in the reverse reaction. The structure of the complex shows a highly interacting intermolecular interface limited to a small area and the proteinbound dihydrolipoyllysine arm inserted into the active site cavity of the T-protein. Invariant Arg^292 of the T-protein is essential for complex assembly. The structure also provides novel insights in understanding the disease-causing mutations, in addition to the disease-related impairment in the cofactor-enzyme interactions reported previously. Furthermore, structural and mutational analyses suggest that the reversible transfer of the methylene group between the lipoate and tetrahydrofolate should proceed through the electron relay-assisted iminium intermediate formation.
Publisher	American Society for Biochemistry and Molecular Biology
Source Title	Journal of Biological Chemistry
Volume (Issue)	285(24)
Page	18684-18692
Date of Issued	2010-06
Language	English
Handle URL	https://hdl.handle.net/11094/73655
eISSN	1083351X
NCID	AA1202441X
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1074/jbc.M110.110718
Relation.isIdenticalTo	PMID 20375021
Access Rights	open access
CopyRight	© the American Society for Biochemistry and Molecular Biology.
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	Journal of Biological Chemistry. 2010, 285(24), p. 18684-18692
DC.title	Crystal structure of aminomethyltransferase in complex with dihydrolipoyl-H-protein of the glycine cleavage system : Implications for recognition of lipoyl protein substrate, disease-related mutations, and reaction mechanism
DC.creator	Okamura, Kazuko
	Hosaka, Harumi
	Maita, Nobuo
	Fujiwara, Kazuko
	Yoshizawa, Akiyasu C.
	Nakagawa, Atushi
	Taniguchi, Hisaaki
DC.creator	Ikeda, Kazuko
DC.publisher	American Society for Biochemistry and Molecular Biology
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2010-06
DC.identifier	https://doi.org/10.1074/jbc.M110.110718
DC.description	This research was originally published in Journal of Biological Chemistry. Kazuko Okamura-Ikeda, Harumi Hosaka, Nobuo Maita, Kazuko Fujiwara, Akiyasu C. Yoshizawa, Atsushi Nakagawa and Hisaaki Taniguchi. Crystal structure of aminomethyltransferase in complex with dihydrolipoyl-H-protein of the glycine cleavage system : Implications for recognition of lipoyl protein substrate, disease-related mutations, and reaction mechanism. Journal of Biological Chemistry. 2010; 285, 18684-18692. © the American Society for Biochemistry and Molecular Biology.
DCTERMS.abstract	Aminomethyltransferase, a component of the glycine cleavage system termed T-protein, reversibly catalyzes the degradation of the aminomethyl moiety of glycine attached to the lipoate cofactor of H-protein, resulting in the production of ammonia, 5,10-methylenetetrahydrofolate, and dihydrolipoate- bearing H-protein in the presence of tetrahydrofolate. Several mutations in the human T-protein gene are known to cause nonketotic hyperglycinemia. Here, we report the crystal structure of Escherichia coli T-protein in complex with dihydrolipoate-bearing H-protein and 5-methyltetrahydrofolate, a complex mimicking the ternary complex in the reverse reaction. The structure of the complex shows a highly interacting intermolecular interface limited to a small area and the proteinbound dihydrolipoyllysine arm inserted into the active site cavity of the T-protein. Invariant Arg^292 of the T-protein is essential for complex assembly. The structure also provides novel insights in understanding the disease-causing mutations, in addition to the disease-related impairment in the cofactor-enzyme interactions reported previously. Furthermore, structural and mutational analyses suggest that the reversible transfer of the methylene group between the lipoate and tetrahydrofolate should proceed through the electron relay-assisted iminium intermediate formation.
DC.rights	© the American Society for Biochemistry and Molecular Biology.
DC.format	73655
citation_title	Crystal structure of aminomethyltransferase in complex with dihydrolipoyl-H-protein of the glycine cleavage system : Implications for recognition of lipoyl protein substrate, disease-related mutations, and reaction mechanism
citation_author	Okamura, Kazuko
	Hosaka, Harumi
	Maita, Nobuo
	Fujiwara, Kazuko
	Yoshizawa, Akiyasu C.
	Nakagawa, Atushi
	Taniguchi, Hisaaki
citation_publisher	American Society for Biochemistry and Molecular Biology
citation_language	English
citation_date	2010-06
citation_journal_title	Journal of Biological Chemistry
citation_volume	285
citation_issue	24
citation_firstpage	18684
citation_lastpage	18692
citation_doi	https://doi.org/10.1074/jbc.M110.110718
citation_pmid	20375021
citation_public_url	https://hdl.handle.net/11094/73655

Crystal structure of aminomethyltransferase in complex with dihydrolipoyl-H-protein of the glycine cleavage system : Implications for recognition of lipoyl protein substrate, disease-related mutations, and reaction mechanism

Link to primary information

Item Information

Show details