NDLI: Crystal Structure of Aminomethyltransferase in Complex with Dihydrolipoyl-H-Protein of the Glycine Cleavage System

Content Provider	PubMed Central
Author	Okamura-ikeda, Kazuko Hosaka, Harumi Maita, Nobuo Fujiwara, Kazuko Yoshizawa, Akiyasu C. Nakagawa, Atsushi Taniguchi, Hisaaki
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 protein-bound dihydrolipoyllysine arm inserted into the active site cavity of the T-protein. Invariant Arg292 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.
Related Links	http://dx.doi.org/10.1074/jbc.m110.110718
Page Count	1
Starting Page	18684
File Format	PDF
ISSN	00219258
e-ISSN	1083351X
Journal	The Journal of Biological Chemistry
Issue Number	24
Volume Number	285
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2010-04-01
Access Restriction	Open
Rights Holder	American Society for Biochemistry and Molecular Biology
Subject Keyword	Cell Biology Biochemistry Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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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

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