Energetic feasibility of hydrogen abstraction and recombination in coenzyme B-12-dependent diol dehydratase reaction

Coenzyme B-12 serves as a cofactor for enzymatic radical reactions. The ess ential steps in all the coenzyme B-12-dependent rearrangements are two hydr ogen abstraction steps: hydrogen abstraction of the adenosyl radical from s ubstrates, and hydrogen back-abstraction (recombination) of a product-deriv ed radical from 5'-deoxyadenosine. The energetic feasibility of these hydro gen abstraction steps in the diol dehyratase reaction was examined by theor etical calculations with a protein-free, simplified model at the B3LYP/6-31 1G' level of density functional theory. Activation energies for the hydroge n abstraction and recombination with 1,2-propanediol as substrate are 9.0 a nd 15.1 kcal/mol, respectively, and essentially not affected by coordinatio n of the substrate and the radical intermediate to K+ Since these energies can be considered to be supplied by the substrate-binding energy, the compu tational results with this simplified model indicate that the hydrogen abst raction and recombination in the coenzyme B12-dependent diol dehydratase re action are energetically feasible.