Stabilization of the adenosyl radical in coenzyme B12 -: a theoretical study

Density functional theory B3LYP calculations have been carried out on a large model for coenzyme B-12. The dissociation curve for the homolytic cleavage of the Co-C bond has been studied for the free cofactor, in the gas phase and including the effect of a dielectric continuum with a dielectric constant of 4.00, as well as in the presence of some key residues present in methylmalonyl-CoA mutase, an enzyme that depends on coenzyme B-12. We describe a hitherto unknown effect of the cofactor which facilitates the homolysis reaction: electrostatic interactions stabilize the radicals formed in this step. H-bonding to protein residues leads to further stabilization. (C) 2004 Elsevier B.V. All rights reserved.