PDBsum entry 3ab9

Transport protein

PDB id: 3ab9

Contents

Protein chain

127 a.a.

Metals

_CL

_CA

Waters ×46

References listed in PDB file

Key reference

• 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.
• Authors: K.Okamura-Ikeda, H.Hosaka, N.Maita, K.Fujiwara, A.C.Yoshizawa, A.Nakagawa, H.Taniguchi.
• Ref.: J Biol Chem, 2010, 285, 18684-18692.
• PubMed id: 20375021

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.