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71  structures 2972  species 5  interactions 8147  sequences 80  architectures

Family: B12-binding (PF02310)

Summary: B12 binding domain

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This is the Wikipedia entry entitled "Vitamin B12-binding domain". More...

Vitamin B12-binding domain Edit Wikipedia article

B12-binding
PDB 1id8 EBI.jpg
nmr structure of glutamate mutase (b12-binding subunit) complexed with the vitamin b12 nucleotide
Identifiers
Symbol B12-binding
Pfam PF02310
InterPro IPR006158
SCOP 1be1
SUPERFAMILY 1be1
B12-binding_2 (4-helical bundle cap domain)
PDB 1bmt EBI.jpg
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
SCOP 1bmt
SUPERFAMILY 1bmt

In molecular biology, the vitamin B12-binding domain is a protein domain which binds to cobalamin (vitamin B12). It can bind two different forms of the cobalamin cofactor, with cobalt bonded either to a methyl group (methylcobalamin) or to 5'-deoxyadenosine (adenosylcobalamin). Cobalamin-binding domains are mainly found in two families of enzymes present in animals and prokaryotes, which perform distinct kinds of reactions at the cobalt-carbon bond. Enzymes that require methylcobalamin carry out methyl transfer reactions. Enzymes that require adenosylcobalamin catalyse 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 a 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] Proteins containing the cobalamin-binding domain include:

The core structure of the cobalamin-binding domain is characterised by a five-stranded alpha/beta (Rossmann) fold, which consists of 5 parallel beta-sheets surrounded by 4-5 alpha helices in three layers (alpha/beta/alpha).[5] Upon binding cobalamin, important elements of the binding site appear to become structured, including an alpha-helix that forms on one side of the cleft accommodating the nucleotide 'tail' of the cofactor. 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 cobalamin-binding domain, the 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.[6] In methionine synthase the cobalamin cofactor is sandwiched between the cobalamin-binding domain and an approximately 90 residues N-terminal domain forming a helical bundle comprising two pairs of antiparallel helices.[6] This N-terminal domain forms a 4-helical bundle cap, 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.[7]

References[edit]

  1. ^ Krautler B (August 2005). "Vitamin B12: chemistry and biochemistry". Biochem. Soc. Trans. 33 (Pt 4): 806–10. doi:10.1042/BST0330806. PMID 16042603. 
  2. ^ Ludwig ML, Matthews RG (1997). "Structure-based perspectives on B12-dependent enzymes". Annu. Rev. Biochem. 66: 269–313. doi:10.1146/annurev.biochem.66.1.269. PMID 9242908. 
  3. ^ Banerjee R, Ragsdale SW (2003). "The many faces of vitamin B12: catalysis by cobalamin-dependent enzymes". Annu. Rev. Biochem. 72: 209–47. doi:10.1146/annurev.biochem.72.121801.161828. PMID 14527323. 
  4. ^ Reitzer R, Gruber K, Jogl G, Wagner UG, Bothe H, Buckel W, Kratky C (August 1999). "Glutamate mutase from Clostridium cochlearium: the structure of a coenzyme B12-dependent enzyme provides new mechanistic insights". Structure 7 (8): 891–902. PMID 10467146. 
  5. ^ Drennan CL, Huang S, Drummond JT, Matthews RG, Lidwig ML (December 1994). "How a protein binds B12: A 3.0 A X-ray structure of B12-binding domains of methionine synthase". Science 266 (5191): 1669–74. doi:10.1126/science.7992050. PMID 7992050. 
  6. ^ a b Mancia F, Keep NH, Nakagawa A, Leadlay PF, McSweeney S, Rasmussen B, Bösecke P, Diat O, Evans PR (March 1996). "How coenzyme B12 radicals are generated: the crystal structure of methylmalonyl-coenzyme A mutase at 2 A resolution". Structure 4 (3): 339–50. PMID 8805541. 
  7. ^ 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): 53–6. doi:10.1038/nsb738. PMID 11731805. 

This article incorporates text from the public domain Pfam and InterPro IPR006158

This article incorporates text from the public domain Pfam and InterPro IPR003759

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

B12 binding domain Provide feedback

This domain binds to B12 (adenosylcobamide)[1-3], it is found in several enzymes, such as glutamate mutase Q05488 methionine synthase Q99707 and methylmalonyl-CoA mutase P22033. It contains a conserved DxHxxGx(41)SxVx(26)GG motif, which is important for B12 binding [2].

Literature references

  1. Tollinger M, Konrat R, Hilbert BH, Marsh EN, Krautler B; , Structure 1998;6:1021-1033.: How a protein prepares for B12 binding: structure and dynamics of the B12-binding subunit of glutamate mutase from Clostridium tetanomorphum. PUBMED:9739092 EPMC:9739092

  2. Cervantes M, Murillo FJ;, J Bacteriol. 2002;184:2215-2224.: Role for vitamin B(12) in light induction of gene expression in the bacterium Myxococcus xanthus. PUBMED:11914353 EPMC:11914353

  3. Perez-Marin MC, Padmanabhan S, Polanco MC, Murillo FJ, Elias-Arnanz M;, Mol Microbiol. 2008;67:804-819.: Vitamin B12 partners the CarH repressor to downregulate a photoinducible promoter in Myxococcus xanthus. PUBMED:18315685 EPMC:18315685


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR006158

The cobalamin (vitamin B12) binding domain can bind two different forms of the cobalamin cofactor, with cobalt bonded either to a methyl group (methylcobalamin) or to 5'-deoxyadenosine (adenosylcobalamin). Cobalamin-binding domains are mainly found in two families of enzymes present in animals and prokaryotes, which perform distinct kinds of reactions at the cobalt-carbon bond. Enzymes that require methylcobalamin carry out methyl transfer reactions. Enzymes that require adenosylcobalamin catalyse 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 a 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 [PUBMED:16042603, PUBMED:9242908, PUBMED:14527323]. Proteins containing the cobalamin-binding domain include:

  • Animal and prokaryotic methionine synthase (EC), which catalyse 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), which are 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).
  • Prokaryotic glutamate mutase (EC) [PUBMED:10467146].
  • Prokaryotic methyleneglutarate mutase (EC).
  • Prokaryotic isobutyryl-CoA mutase (EC).

The core structure of the cobalamin-binding domain is characterised by a five-stranded alpha/beta (Rossmann) fold, which consists of 5 parallel beta-sheets surrounded by 4-5 alpha helices in three layers (alpha/beta/alpha) [PUBMED:7992050]. Upon binding cobalamin, important elements of the binding site appear to become structured, including an alpha-helix that forms on one side of the cleft accommodating the nucleotide 'tail' of the cofactor. 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 cobalamin-binding domain, the 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 [PUBMED:8805541]. In methionine synthase the cobalamin cofactor is sandwiched between the cobalamin-binding domain and an approximately 90 residues N-terminal domain forming a helical bundle comprising two pairs of antiparallel helices [PUBMED:8805541].

In methionine synthase, there is a second, adjacent domain involved in cobalamin binding that forms a 4-helical bundle cap (INTERPRO); 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) [PUBMED:11731805].

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Domain organisation

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Full
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Representative proteomes NCBI
(7333)
Meta
(2597)
RP15
(1180)
RP35
(2176)
RP55
(2679)
RP75
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  Seed
(133)
Full
(8147)
Representative proteomes NCBI
(7333)
Meta
(2597)
RP15
(1180)
RP35
(2176)
RP55
(2679)
RP75
(3031)
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Curation and family details

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Curation View help on the curation process

Seed source: Pfam-B_359 (release 5.2)
Previous IDs: none
Type: Domain
Author: Bateman A, Mian N
Number in seed: 133
Number in full: 8147
Average length of the domain: 115.00 aa
Average identity of full alignment: 22 %
Average coverage of the sequence by the domain: 16.83 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 28.0 28.0
Trusted cut-off 28.0 28.0
Noise cut-off 27.9 27.9
Model length: 121
Family (HMM) version: 14
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Interactions

There are 5 interactions for this family. More...

Met_asp_mut_E Met_synt_B12 MM_CoA_mutase B12-binding_2 Lys-AminoMut_A

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the B12-binding domain has been found. There are 71 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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