IntEnz

EC 2.5.1.151 - Alkylcobalamin dealkylase

IntEnz Enzyme Nomenclature
EC 2.5.1.151

Names

Reaction

• 40719 [IUBMB]
  an alkylcob(III)alamin

  an alkylcob(III)alamin

  Name origin: UniProt - CHECKED (C)

  CHEBI:140785

  Formula: C62H88CoN13O14PR
  Charge: 0

  ChEBI compound status: SUBMITTED (S)

  

  +

  apo--[alkylcobalamin reductase]

  apo--[alkylcobalamin reductase]

  GENERIC:14731

  Is ROOT: no
  ROOT compound: GENERIC:14716

  Number of residues: 1

  an L-α amino acid residue an L-alpha amino acid residue Name origin: UniProt - CHECKED (C) CHEBI:83228 Formula: C2H2NOR Charge: 0 Position: undefined ChEBI compound status: CHECKED (C)

  +

  glutathione

  glutathione

  Name origin: UniProt - CHECKED (C)

  CHEBI:57925

  Formula: C10H16N3O6S
  Charge: -1

  ChEBI compound status: CHECKED (C)

  

  =

  an S-substituted glutathione

  an S-substituted glutathione

  Name origin: UniProt - CHECKED (C)

  CHEBI:90779

  Formula: C10H15N3O6SR
  Charge: -1

  ChEBI compound status: CHECKED (C)

  

  +

  cob(I)alamin—[alkylcobalamin reductase]

  cob(I)alamin--[alkylcobalamin reductase]

  GENERIC:14730

  Is ROOT: no
  ROOT compound: GENERIC:14716

  Number of residues: 2

  cob(I)alamin cob(I)alamin Name origin: UniProt - CHECKED (C) CHEBI:60488 Formula: C62H88CoN13O14P Charge: -1 Position: A ChEBI compound status: CHECKED (C)

  an L-α amino acid residue an L-alpha amino acid residue Name origin: UniProt - CHECKED (C) CHEBI:83228 Formula: C2H2NOR Charge: 0 Position: B ChEBI compound status: CHECKED (C)

  +

  H⁺

  H(+)

  Name origin: UniProt - CHECKED (C)

  CHEBI:15378

  Formula: H
  Charge: 1

  ChEBI compound status: CHECKED (C)

  

Comments:

This mammalian enzyme, which is cytosolic, can bind internalized alkylcobalamins and process them to cob(I)alamin using the thiolate of glutathione for nucleophilic displacement. The product remains bound to the protein, and, following its oxidation to cob(II)alamin, is transferred by the enzyme, together with its interacting partner MMADHC, directly to downstream enzymes involved in adenosylcobalamin and methylcobalamin biosynthesis. In addition to its dealkylase function, the enzyme also catalyse an entirely different decyanase reaction with cyanocobalamin [cf. EC 1.16.1.6, cyanocobalamin reductase (cyanide-eliminating)].

Links to other databases

References

1. Hannibal, L., Kim, J., Brasch, N. E., Wang, S., Rosenblatt, D. S., Banerjee, R., Jacobsen, D. W.
   Processing of alkylcobalamins in mammalian cells: A role for the MMACHC (cblC) gene product.
   Mol. Genet. Metab. 97: 260-266 (2009). [PMID: 19447654]
2. Kim, J., Hannibal, L., Gherasim, C., Jacobsen, D. W., Banerjee, R.
   A human vitamin B12 trafficking protein uses glutathione transferase activity for processing alkylcobalamins.
   J. Biol. Chem. 284: 33418-33424 (2009). [PMID: 19801555]
3. Koutmos, M., Gherasim, C., Smith, J. L., Banerjee, R.
   Structural basis of multifunctionality in a vitamin B12-processing enzyme.
   J. Biol. Chem. 286: 29780-29787 (2011). [PMID: 21697092]

[EC 2.5.1.151 created 2018]