3A8I: Crystal Structure Of Et-ehred-5-ch3-thf Complex

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.
PDB ID: 3A8IDownload
MMDB ID: 81205
PDB Deposition Date: 2009/10/6
Updated in MMDB: 2013/08
Experimental Method:
x-ray diffraction
Resolution: 1.99  Å
Source Organism:
Similar Structures:
Biological Unit for 3A8I: dimeric; determined by author
Molecular Components in 3A8I
Label Count Molecule
Proteins (2 molecules)
Aminomethyltransferase(Gene symbol: gcvT)
Molecule annotation
Glycine Cleavage System H Protein(Gene symbol: gcvH)
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB