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80  structures 10995  species 10  interactions 26325  sequences 107  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

  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. doi:10.1016/s0969-2126(99)80116-6. 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. doi:10.1016/s0969-2126(96)00037-8. 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].

Gene Ontology

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Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan NADP_Rossmann (CL0063), which has the following description:

A class of redox enzymes are two domain proteins. One domain, termed the catalytic domain, confers substrate specificity and the precise reaction of the enzyme. The other domain, which is common to this class of redox enzymes, is a Rossmann-fold domain. The Rossmann domain binds nicotinamide adenine dinucleotide (NAD+) and it is this cofactor that reversibly accepts a hydride ion, which is lost or gained by the substrate in the redox reaction. Rossmann domains have an alpha/beta fold, which has a central beta sheet, with approximately five alpha helices found surrounding the beta sheet.The strands forming the beta sheet are found in the following characteristic order 654123. The inter sheet crossover of the stands in the sheet form the NAD+ binding site [1]. In some more distantly relate Rossmann domains the NAD+ cofactor is replaced by the functionally similar cofactor FAD.

The clan contains the following 181 members:

2-Hacid_dh_C 3Beta_HSD 3HCDH_N adh_short adh_short_C2 ADH_zinc_N ADH_zinc_N_2 AdoHcyase_NAD AdoMet_MTase AlaDh_PNT_C Amino_oxidase ApbA AviRa B12-binding Bac_GDH Bin3 CheR CMAS CmcI CoA_binding CoA_binding_2 CoA_binding_3 Cons_hypoth95 DAO DapB_N DFP DNA_methylase DOT1 DREV DUF1442 DUF166 DUF1776 DUF2431 DUF268 DUF3321 DUF364 DUF43 DUF938 DXP_redisom_C DXP_reductoisom Eco57I ELFV_dehydrog Eno-Rase_FAD_bd Eno-Rase_NADH_b Enoyl_reductase Epimerase F420_oxidored FAD_binding_2 FAD_binding_3 FAD_oxidored Fibrillarin FMO-like FmrO FtsJ G6PD_N GCD14 GDI GDP_Man_Dehyd GFO_IDH_MocA GIDA GidB GLF Glu_dehyd_C Glyco_hydro_4 GMC_oxred_N Gp_dh_N GRAS GRDA HI0933_like HIM1 IlvN K_oxygenase KR LCM Ldh_1_N Lycopene_cycl Malic_M Mannitol_dh MCRA Met_10 Methyltrans_Mon Methyltrans_SAM Methyltransf_10 Methyltransf_11 Methyltransf_12 Methyltransf_15 Methyltransf_16 Methyltransf_17 Methyltransf_18 Methyltransf_19 Methyltransf_2 Methyltransf_20 Methyltransf_21 Methyltransf_22 Methyltransf_23 Methyltransf_24 Methyltransf_25 Methyltransf_26 Methyltransf_28 Methyltransf_29 Methyltransf_3 Methyltransf_30 Methyltransf_31 Methyltransf_32 Methyltransf_34 Methyltransf_4 Methyltransf_5 Methyltransf_7 Methyltransf_8 Methyltransf_9 Methyltransf_PK MethyltransfD12 MetW Mg-por_mtran_C Mqo MT-A70 MTS Mur_ligase N2227 N6-adenineMlase N6_Mtase N6_N4_Mtase NAD_binding_10 NAD_binding_2 NAD_binding_3 NAD_binding_4 NAD_binding_5 NAD_binding_7 NAD_binding_8 NAD_binding_9 NAD_Gly3P_dh_N NAS NmrA NNMT_PNMT_TEMT NodS Nol1_Nop2_Fmu NSP13 OCD_Mu_crystall PARP_regulatory PCMT PDH Polysacc_synt_2 Pox_MCEL Prenylcys_lyase PrmA PRMT5 Pyr_redox Pyr_redox_2 Pyr_redox_3 RmlD_sub_bind Rossmann-like rRNA_methylase RrnaAD Rsm22 RsmJ Sacchrp_dh_NADP SAM_MT SAMBD SE Semialdhyde_dh Shikimate_DH Spermine_synth TehB THF_DHG_CYH_C Thi4 ThiF TPMT TrkA_N TRM TRM13 TrmK tRNA_U5-meth_tr Trp_halogenase TylF Ubie_methyltran UDPG_MGDP_dh_N UPF0020 UPF0146 V_cholerae_RfbT XdhC_C YjeF_N

Alignments

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  Seed
(92)
Full
(26325)
Representative proteomes NCBI
(18934)
Meta
(2567)
RP15
(1092)
RP35
(2642)
RP55
(3843)
RP75
(4784)
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  Seed
(92)
Full
(26325)
Representative proteomes NCBI
(18934)
Meta
(2567)
RP15
(1092)
RP35
(2642)
RP55
(3843)
RP75
(4784)
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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

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: 92
Number in full: 26325
Average length of the domain: 114.20 aa
Average identity of full alignment: 26 %
Average coverage of the sequence by the domain: 15.05 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 80369284 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 28.2 28.2
Trusted cut-off 28.2 28.2
Noise cut-off 28.1 28.1
Model length: 121
Family (HMM) version: 15
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Interactions

There are 10 interactions for this family. More...

B12-binding_2 Lys-AminoMut_A Met_asp_mut_E Met_synt_B12 B12-binding Lys-AminoMut_A MM_CoA_mutase MtaB MM_CoA_mutase MtaB

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 80 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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