From Synthetic to Biological Fe4 S4 Complexes: Redox Properties Correlated to Function of Radical S-Adenosylmethionine Enzymes.

By employing the computational protocol for calculation of reduction potentials of the Fe4 S4 -containing species validated using a representative series of well-defined synthetic complexes, we focused on redox properties of two prototypical radical SAM enzymes to reveal how they transform SAM into the reactive 5'-deoxyadenosyl radical, and how they tune this radical for its proper biological function. We found the reduction potential of SAM is indeed elevated by 0.3-0.4 V upon coordination to Fe4 S4 , which was previously speculated in the literature. This makes a generation of 5'-deoxyadenosyl radical from SAM less endergonic (by ca. 7-9 kcal mol-1 ) and hence more feasible in both enzymes as compared to the identical process in water. Furthermore, our calculations indicate that the enzyme-bound 5'-deoxyadenosyl radical has a significantly lower reduction potential than in referential aqueous solution, which may help the enzymes to suppress potential side redox reactions and simultaneously elevate its proton-philic character, which may, in turn, promote the radical hydrogen-atom abstraction ability.