G3DSA:3.10.196.10

Vitamin B12-dependent methionine synthase, activation domain

CATH-Gene3D entry
Member databaseCATH-Gene3D
CATH-Gene3D typehomologous superfamily

Description
Imported from IPR037010

Vitamin B12 dependent methionine synthase
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 inde novomethionine 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
[1]
. The activation domain adopts an unusual α/β fold.

References
Imported from IPR037010

1.Domain alternation switches B(12)-dependent methionine synthase to the activation conformation. Bandarian V, Pattridge KA, Lennon BW, Huddler DP, Matthews RG, Ludwig ML. Nat. Struct. Biol. 9, 53-6, (2002). View articlePMID: 11731805

This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our Privacy Notice and Terms of Use.