PMID:20375021
| Citation |
Okamura-Ikeda, K, Hosaka, H, Maita, N, Fujiwara, K, Yoshizawa, AC, Nakagawa, A and Taniguchi, H (2010) 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. J. Biol. Chem. 285:18684-92 |
|---|---|
| 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 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. |
| Links |
PubMed PMC2881793 Online version:10.1074/jbc.M110.110718 |
| Keywords |
Aminomethyltransferase/chemistry; Arginine/chemistry; Bacterial Proteins/chemistry; Catalysis; Catalytic Domain; Crystallography, X-Ray/methods; DNA Mutational Analysis; DNA-Binding Proteins/chemistry; Dimerization; Escherichia coli/metabolism; Folic Acid/chemistry; Glycine/chemistry; Hyperglycemia/metabolism; Imines/chemistry; Models, Molecular; Mutation |
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