PROSITE documentation PDOC51332 [for PROSITE entry PS51337]

B12-binding and B12-binding N-terminal domain profiles




Description

The B12-binding domain is mainly found in two families of enzymes present in animals and prokaryotes, which use vitamin B12 (cobalamin) as cofactor. The B12-binding domain can bind two different forms of the cobalamin cofactor, with cobalt bonded either to a methyl group or to 5'-deoxyadenosine. Methyl- and adenosylcobalamin enzymes perform distinct kinds of reactions at the cobalt-carbon bond. The enzymes that bind methylcobalamin carry out methyl transfer reactions. Enzymes that require adenosylcobalamin catalyze reactions in which the first step is the cleavage of adenosylcobalamin to form cob(II)alamin and the 5'-deoxyadenosyl radical and thus act as radical generators. In both types of enzymes the B12-binding domain uses an histidine to bind the cobalt atom of cobalamin cofactors. This histidine is embedded in a DXHXXG sequence, the most conserved primary sequence motif of the domain [1,2,3].

The structure of the B12-binding domain is characterised by a five-stranded α/β (Rossmann) fold (see <PDB:1BMT>) [4]. In cobalamin the cobalt atom can be either free (dmb-off) or bound to dimethylbenzimidazole (dmb-on) according to the pH. When bound to the B12-binding domain dimethylbenzimidazole ligand is replaced by the active histidine (His-on) of the DXHXXG motif. The replacement of dimethylbenzimidazole by histidine allows switching between the catalytic and activation cycles [5]. In methionine synthase the cobalamin cofactor is sandwiched between the B12-binding domain and an ~90 residues N-terminal domain forming a helical bundle comprising two pairs of antiparallel helices [4].

The B12-binding domain is found in the following enzymes:

  • Animal and prokaryotic methionine synthase (EC 2.1.1.13). It catalyzes the transfer of a methyl group from methyl-cobalamin to homocysteine, yielding enzyme-bound cob(I)alamin and methionine.
  • Animal and prokaryotic methylmalonyl-CoA mutase (EC 5.4.99.2). It is involved in the degradation of several amino acids, odd-chain fatty acids and cholesterol via propionyl-CoA to the tricarboxylic acid cycle.
  • Prokaryotic lysine 5,6-aminomutase (EC 5.4.3.4).
  • Prokaryotic glutamate mutase (EC 5.4.99.1).
  • Prokaryotic methyleneglutarate mutase (EC 5.4.99.4).
  • Prokaryotic isobutyryl-CoA mutase (EC 5.4.99.13).

The first profile recognizes the whole B12-binding domain. The second one is directed against the helical bundle found N-terminal to the B12-binding domain of methionine synthase.

Last update:

November 2007 / First entry.

Technical section

PROSITE methods (with tools and information) covered by this documentation:

B12_BINDING_NTER, PS51337; B12-binding N-terminal domain profile  (MATRIX)

B12_BINDING, PS51332; B12-binding domain profile  (MATRIX)


References

1AuthorsKrautler B.
TitleVitamin B12: chemistry and biochemistry.
SourceBiochem. Soc. Trans. 33:806-810(2005).
PubMed ID16042603
DOI10.1042/BST0330806

2AuthorsLudwig M.L., Matthews R.G.
TitleStructure-based perspectives on B12-dependent enzymes.
SourceAnnu. Rev. Biochem. 66:269-313(1997).
PubMed ID9242908
DOI10.1146/annurev.biochem.66.1.269

3AuthorsBanerjee R., Ragsdale S.W.
TitleThe many faces of vitamin B12: catalysis by cobalamin-dependent enzymes.
SourceAnnu. Rev. Biochem. 72:209-247(2003).
PubMed ID14527323
DOI10.1146/annurev.biochem.72.121801.161828

4AuthorsMancia F., Keep N.H., Nakagawa A., Leadlay P.F., McSweeney S., Rasmussen B., Bosecke P., Diat O., Evans P.R.
TitleHow coenzyme B12 radicals are generated: the crystal structure of methylmalonyl-coenzyme A mutase at 2 A resolution.
SourceStructure 4:339-350(1996).
PubMed ID8805541

5AuthorsMancia F., Keep N.H., Nakagawa A., Leadlay P.F., McSweeney S., Rasmussen B., Bosecke P., Diat O., Evans P.R.
TitleHow coenzyme B12 radicals are generated: the crystal structure of methylmalonyl-coenzyme A mutase at 2 A resolution.
SourceStructure 4:339-350(1996).
PubMed ID8805541



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