Crystal structure of precorrin-8x methyl mutase

Structure. 2001 Jul 3;9(7):587-96. doi: 10.1016/s0969-2126(01)00618-9.


Background: The crystal structure of precorrin-8x methyl mutase (CobH), an enzyme of the aerobic pathway to vitamin B12, provides evidence that the mechanism for methyl migration can plausibly be regarded as an allowed [1,5]-sigmatropic shift of a methyl group from C-11 to C-12 at the C ring of precorrin-8x to afford hydrogenobyrinic acid.

Results: The dimeric structure of CobH creates a set of shared active sites that readily discriminate between different tautomers of precorrin-8x and select a discrete tautomer for sigmatropic rearrangement. The active site contains a strictly conserved histidine residue close to the site of methyl migration in ring C of the substrate.

Conclusion: Analysis of the structure with bound product suggests that the [1,5]-sigmatropic shift proceeds by protonation of the ring C nitrogen, leading to subsequent methyl migration.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins*
  • Base Sequence
  • Binding Sites
  • Crystallography, X-Ray
  • Intramolecular Transferases / chemistry*
  • Intramolecular Transferases / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Sequence Homology, Amino Acid
  • Substrate Specificity
  • Uroporphyrins / chemistry
  • Uroporphyrins / metabolism


  • Bacterial Proteins
  • Uroporphyrins
  • hydrogenobyrinic acid
  • Intramolecular Transferases
  • CobH protein, Pseudomonas denitrificans

Associated data

  • PDB/1F2V
  • PDB/1I1H