3A8K

Crystal Structure of ETD97N-EHred complex

Summary for 3A8K

• Entry DOI: 10.2210/pdb3a8k/pdb
• Related: 1WSR 1WSV 3A8I 3A8J
• Descriptor: Aminomethyltransferase, Glycine cleavage system H protein (3 entities in total)
• Functional Keywords: glycine cleavage system, aminotransferase, transferase, lipoyl, transferase-transport protein complex, transferase/transport protein
• Biological source: Escherichia coli; More
• Total number of polymer chains: 6
• Total formula weight: 188777.30

Authors

Okamura-Ikeda, K.,Hosaka, H. (deposition date: 2009-10-06, release date: 2010-04-07, Last modification date: 2023-11-01)

Primary citation

Okamura-Ikeda, K.,Hosaka, H.,Maita, N.,Fujiwara, K.,Yoshizawa, A.C.,Nakagawa, A.,Taniguchi, H.
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., 285:18684-18692, 2010

PubMed 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.

PubMed: 20375021
DOI: 10.1074/jbc.M110.110718

Experimental method

X-RAY DIFFRACTION (1.95 Å)