engleski

The Elusive 5'-Deoxyadenosyl Radical in Coenzyme-B12-Mediated Reactions

Enzymes that rely on coenzyme B12 (5’-deoxyadenosylcobalamin) have generated a great deal of interest in the scientific community. One particular focus has been the activation of the Co–C bond of the coenzyme and its connection to the subsequent hydrogen-atom abstraction from the substrate. In this contribution, we address these steps with a state-of-the-art QM/MM first principles molecular dynamics study of the methylmalonyl-CoA mutase catalyzed reaction. Using techniques such as constrained- and meta-dynamics, we evaluate the free energy profiles and surfaces associated with the coenzyme cleavage and the substrate activation. By further analyzing the dynamics of the natural cofactor and two synthetic analogues, we shed new light on the important catalytic effects as well as the way in which the enzyme controls the highly reactive 5’-deoxyadenosyl radical intermediate.

Coenzyme B12; QM/MM

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