J. Heyrovský Institute of Physical Chemistry, Czech Academy of Sciences, Dolejškova 3, Prague, 8 182 23, Czech Republic.
Chempluschem. 2020 Nov;85(11):2534-2541. doi: 10.1002/cplu.202000663.
By employing the computational protocol for calculation of reduction potentials of the Fe S -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 Fe S , 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 ) 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.
我们采用了一种经过代表性的一系列结构明确的合成配合物验证的含 Fe-S 物种还原电势的计算方案，重点研究了两种典型的自由基 SAM 酶的氧化还原性质，以揭示它们如何将 SAM 转化为反应性的 5'-脱氧腺苷自由基，以及它们如何调整这种自由基以实现其适当的生物学功能。我们发现，SAM 与 Fe-S 配位后，其还原电势确实升高了 0.3-0.4 V，这在文献中曾有推测。这使得从 SAM 生成 5'-脱氧腺苷自由基的过程在这两种酶中比在水中更具可行性（大约减少 7-9 kcal/mol）。此外，我们的计算表明，与参考的水溶液相比，酶结合的 5'-脱氧腺苷自由基的还原电势显著降低，这可能有助于酶抑制潜在的副氧化还原反应，并同时提高其质子亲核性，这反过来又可能促进自由基的氢原子夺取能力。
