Crystal structure of precorrin-8x methyl mutase.
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.


CONCLUSIONS
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.
Shipman
L W
LW
Department of Chemistry, Texas A&M University, College Station, TX 77843, USA. sacchett@tamu.edu
Li
D
D
Roessner
C A
CA
Scott
A I
AI
Sacchettini
J C
JC
D000595:Amino Acid Sequence; D001426:Bacterial Proteins; D001483:Base Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D019751:Intramolecular Transferases / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D014578:Uroporphyrins / Q000737:chemistry / Q000378:metabolism
D001426:Bacterial Proteins; D014578:Uroporphyrins; C072476:hydrogenobyrinic acid; D019751:Intramolecular Transferases; C072474:CobH protein, Pseudomonas denitrificans