From Synthetic to Biological Fe4S4 Complexes: Redox Properties Correlated to Function of Radical S-Adenosylmethionine Enzymes
From Synthetic to Biological Fe4S4 Complexes: Redox Properties Correlated to Function of Radical S-Adenosylmethionine Enzymes
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DOI：
10.1002/cplu.202000663
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发表时间：
2020-11-01
期刊：
影响因子：
3.4
通讯作者：
Srnec, Martin
中科院分区：
文献类型：
--
作者：
Bim, Daniel;Alonso-Gil, Santiago;Srnec, Martin
通过采用计算协议的Fe 4S 4-含物种的还原电位的计算验证使用一系列有代表性的定义明确的合成复合物，我们专注于两个原型自由基SAM酶的氧化还原特性，以揭示他们如何将SAM转化为反应性的5 '-脱氧腺苷自由基，以及他们如何调整这个自由基，其适当的生物功能。我们发现，SAM的还原电位确实提高了0.3-0.4 V后，协调到Fe 4S 4，这是以前在文献中推测。这使得来自SAM的5 '-脱氧腺苷自由基的产生不那么吸能（通过约。7-9 kcal mol（-1）），因此与水中的相同方法相比，在两种酶中更可行。此外，我们的计算表明，酶结合的5 '-脱氧腺苷自由基具有显着低于参考水溶液中的还原电位，这可能有助于酶抑制潜在的副氧化还原反应，同时提高其亲质子性，这可能，反过来，促进自由基的氢原子提取能力。
By employing the computational protocol for calculation of reduction potentials of the Fe4S4-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 Fe4S4, 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.