Member database | PROSITE profiles |
PROSITE profiles type | domain |
Short name | B12_BINDING |
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
[2][1][4].
The structure of the B12-binding domain is characterised by a five-stranded
alpha/beta (Rossmann) fold
[3]. 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
[3]. 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
[3].
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.
References
1.Structure-based perspectives on B12-dependent enzymes. Ludwig ML, Matthews RG. Annu. Rev. Biochem. 66, 269-313, (1997). View articlePMID: 9242908
2.Vitamin B12: chemistry and biochemistry. Krautler B. Biochem. Soc. Trans. 33, 806-10, (2005). View articlePMID: 16042603
3.How coenzyme B12 radicals are generated: the crystal structure of methylmalonyl-coenzyme A mutase at 2 A resolution. Mancia F, Keep NH, Nakagawa A, Leadlay PF, McSweeney S, Rasmussen B, Bosecke P, Diat O, Evans PR. Structure 4, 339-50, (1996). View articlePMID: 8805541
4.The many faces of vitamin B12: catalysis by cobalamin-dependent enzymes. Banerjee R, Ragsdale SW. Annu. Rev. Biochem. 72, 209-47, (2003). View articlePMID: 14527323