Domain

Vitamin B12-dependent methionine synthase, activation domain (IPR004223)

Short name: VitB12-dep_Met_synth_activ_dom

Domain relationships

None.

Description

Vitamin B12 dependent methionine synthase EC:2.1.1.13 (5-methyltetrahydrofolate--homocysteine S-methyltransferase) catalyses the conversion of 5-methyltetrahydrofolate and L-homocysteine to tetrahydrofolate and L-methionine as the final step in de novo methionine biosynthesis. The enzyme requires methylcobalamin as a cofactor. In humans, defects in this enzyme are the cause of autosomal recessive inherited methylcobalamin deficiency (CBLG), which causes mental retardation, macrocytic anemia and homocystinuria. Mild deficiencies in activity may result in mild hyperhomocysteinemia, and mutations in the enzyme may be involved in tumorigenesis. Vitamin B12 dependent methionine synthase is found in prokaryotes and eukaryotes, but in prokaryotes the cofactor is cobalamin.

In Escherichia coli, methionine synthase is a large enzyme composed of four structurally and functionally distinct modules: the first two modules bind homocysteine and tetrahydrofolate, the third module binds the B12 cofactor (IPR003759, IPR006158), and the C-terminal module (activation domain) binds S-adenosylmethionine. The activation domain is essential for the reductive activation of the enzyme. During the catalytic cycle, the highly reactive cob(I)alamin intermediate can be oxidised to produce an inactive cob(II)alamin enzyme; the enzyme is then reactivated via reductive methylation by the activation domain [PMID: 11731805]. The activation domain adopts an unusual alpha/beta fold.

GO terms

Biological Process

GO:0009086 methionine biosynthetic process

Molecular Function

GO:0008705 methionine synthase activity

Cellular Component

GO:0005622 intracellular

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
SUPERFAMILY
Pfam
GENE3D
PROSITE profiles