Crystal Structure of Precorrin-8x Methyl Mutase
2001; Elsevier BV; Volume: 9; Issue: 7 Linguagem: Inglês
10.1016/s0969-2126(01)00618-9
ISSN1878-4186
AutoresLance W. Shipman, Ding Li, Charles A. Roessner, A. Ian Scott, James C. Sacchettini,
Tópico(s)Biochemical and Molecular Research
ResumoBackground: 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 [1Li Y. Battersby A.R. et al.Biosynthesis of vitamin B12 - mechanistic studies on the transfer of a methyl group from C-11 to C-12 and incorporation of O-18.J. Chem. Soc., Chem. Comm. 1994; 21: 2507-2508Crossref Google Scholar, 5Blanche F. Muller G. et al.Hydrogenobyrinic acid isolation, biosynthesis, and function.Angew. Chem. Int. Ed. Engl. 1990; 29: 884-886Crossref Scopus (26) Google Scholar]-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 [1Li Y. Battersby A.R. et al.Biosynthesis of vitamin B12 - mechanistic studies on the transfer of a methyl group from C-11 to C-12 and incorporation of O-18.J. Chem. Soc., Chem. Comm. 1994; 21: 2507-2508Crossref Google Scholar, 5Blanche F. Muller G. et al.Hydrogenobyrinic acid isolation, biosynthesis, and function.Angew. Chem. Int. Ed. Engl. 1990; 29: 884-886Crossref Scopus (26) Google Scholar]-sigmatropic shift proceeds by protonation of the ring C nitrogen, leading to subsequent methyl migration.
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