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.
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 Cnitrogen, leading to subsequent methyl migration.
Authors: Christopher K Prier; Todd K Hyster; Christopher C Farwell; Audrey Huang; Frances H Arnold Journal: Angew Chem Int Ed Engl Date: 2016-03-11 Impact factor: 15.336
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Authors: Evelyne Deery; Susanne Schroeder; Andrew D Lawrence; Samantha L Taylor; Arefeh Seyedarabi; Jitka Waterman; Keith S Wilson; David Brown; Michael A Geeves; Mark J Howard; Richard W Pickersgill; Martin J Warren Journal: Nat Chem Biol Date: 2012-10-07 Impact factor: 15.040
Authors: Andrew D Lawrence; Emi Nemoto-Smith; Evelyne Deery; Joseph A Baker; Susanne Schroeder; David G Brown; Jennifer M A Tullet; Mark J Howard; Ian R Brown; Alison G Smith; Helena I Boshoff; Clifton E Barry; Martin J Warren Journal: Cell Chem Biol Date: 2018-05-17 Impact factor: 8.116