Domain

Cobalamin (vitamin B12)-binding module, cap domain (IPR003759)

Short name: Cbl-bd_cap

Domain relationships

None.

Description

Cobalamin-dependent methionine synthase (EC:2.1.1.13) is a large modular protein that catalyses methyl transfer from methyltetrahydrofolate (CH3-H4folate) to homocysteine. During the catalytic cycle, it supports three distinct methyl transfer reactions, each involving the cobalamin (vitamin B12) cofactor and a substrate bound to its own functional unit [PMID: 11731805]. The cobalamin cofactor plays an essential role in this reaction, accepting the methyl group from CH3-H4folate to form methylcob(III)alamin, and in turn donating the methyl group to homocysteine to generate methionine and cob(I)alamin.

Methionine synthase is a large enzyme composed of four structurally and functionally distinct modules: the first two modules bind homocysteine and CH3-H4folate, the third module binds the cobalamin cofactor and the C-terminal module binds S-adenosylmethionine. The cobalamin-binding module is composed of two structurally distinct domains: a 4-helical bundle cap domain (residues 651-740 in the Escherichia coli enzyme) and an alpha/beta B12-binding domain (residues 741-896) (IPR006158). The 4-helical bundle forms a cap over the alpha/beta domain, which acts to shield the methyl ligand of cobalamin from solvent [PMID: 8939751]. Furthermore, in the conversion to the active conformation of this enzyme, the 4-helical cap rotates to allow the cobalamin cofactor to bind the activation domain (IPR004223). The alpha/beta domain is a common cobalamin-binding motif, whereas the 4-helical bundle domain with its methyl cap is a distinctive feature of methionine synthases.

This entry represents the 4-helical bundle cap domain. This domain is also present in other shorter proteins that bind to B12, and is always found N terminus to the alpha/beta B12-binding domain.

GO terms

Biological Process

GO:0009086 methionine biosynthetic process

Molecular Function

GO:0031419 cobalamin binding
GO:0046872 metal ion binding
GO:0008705 methionine synthase activity

Cellular Component

No terms assigned in this category.

Contributing signatures

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