User:Cboursnell/Sandbox/Z/B12-binding 2
| B12-binding_2 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 how a protein binds b12: a 3.o angstrom x-ray structure of the b12-binding domains of methionine synthase | |||||||||
| Identifiers | |||||||||
| Symbol | B12-binding_2 | ||||||||
| Pfam | PF02607 | ||||||||
| InterPro | IPR003759 | ||||||||
| SCOP2 | 1bmt / SCOPe / SUPFAM | ||||||||
| |||||||||
Cobalamin-dependent methionine synthase (EC) 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.[1] 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) (INTERPRO). The 4-helical bundle forms a cap over the alpha/beta domain, which acts to shield the methyl ligand of cobalamin from solvent.[2] 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 (INTERPRO). 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.
References
[edit]- ^ Bandarian V, Pattridge KA, Lennon BW, Huddler DP, Matthews RG, Ludwig ML (January 2002). "Domain alternation switches B(12)-dependent methionine synthase to the activation conformation". Nat. Struct. Biol. 9 (1): 53–56. doi:10.1038/nsb738. PMID 11731805.
{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link) - ^ Dixon MM, Huang S, Matthews RG, Ludwig M (November 1996). "The structure of the C-terminal domain of methionine synthase: presenting S-adenosylmethionine for reductive methylation of B12". Structure. 4 (11): 1263–1275. doi:10.1016/s0969-2126(96)00135-9. PMID 8939751.
{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)