Energetic feasibility of hydrogen abstraction and recombination in coenzyme B₁₂-dependent diol dehydratase reaction

Coenzyme B₁₂ serves as a cofactor for enzymatic radical reactions. The essential steps in all the coenzyme B₁₂-dependent rearrangements are two hydrogen abstraction steps: Hydrogen abstraction of the adenosyl radical from substrates, and hydrogen back abstraction (recombination) of a product-derived radical from 5′-deoxyadenosine. The energetic feasibility of these hydrogen abstraction steps in the diol dehyratase reaction was examined by theoretical calculations with a protein-free, simplified model at the B3LYP/6-311G* level of density functional theory. Activation energies for the hydrogen abstraction and recombination with 1,2-propanediol as substrate are 9.0 and 15.1 kcal/mol, respectively, and essentially not affected by coordination of the substrate and the radical intermediate to K⁺. Since these energies can be considered to be supplied by the substrate-binding energy, the computational results with this simplified model indicate that the hydrogen abstraction and recombination in the coenzyme B₁₂-dependent diol dehydratase reaction are energetically feasible.