PDBsum entry 3ab9

Transport protein

PDB id: 3ab9

Contents

Protein chain

127 a.a. *

Metals

_CL

_CA

Waters ×46

* Residue conservation analysis

PDB id:

3ab9

Name:

Transport protein

Title:

Crystal structure of lipoylated e. Coli h-protein (reduced form)

Structure:

Glycine cleavage system h protein. Chain: a. Engineered: yes

Source:

Escherichia coli. Organism_taxid: 83333. Strain: k-12 substr. W3110. Gene: gcvh. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.65Å R-factor: 0.205 R-free: 0.216

Authors:

K.Okamura-Ikeda,N.Maita

Key ref:

K.Okamura-Ikeda et al. (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, 18684-18692. PubMed id: 20375021

Date:

04-Dec-09 Release date: 07-Apr-10

Protein chain

P0A6T9  (GCSH_ECOLI) -  Glycine cleavage system H protein from Escherichia coli (strain K12)

Seq: 129 a.a.

Struc: 127 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

J Biol Chem 285:18684-18692 (2010)

PubMed id: 20375021

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.

K.Okamura-Ikeda, H.Hosaka, N.Maita, K.Fujiwara, A.C.Yoshizawa, A.Nakagawa, H.Taniguchi.

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.