Analysis of Electrochemical Properties of S-Adenosyl-l-methionine and Implications for Its Role in Radical SAM Enzymes.
Analysis of Electrochemical Properties of S-Adenosyl-l-methionine and Implications for Its Role in Radical SAM Enzymes.
复制标题
S-腺苷-L-甲硫氨酸的电化学性质分析及其在自由基 SAM 酶中的作用的意义。
DOI：
10.1021/jacs.9b00933
复制
发表时间：
2019
影响因子：
15
通讯作者：
Bandarian,Vahe
中科院分区：
文献类型：
--
作者：
Miller,SvenA;Bandarian,Vahe
S-腺苷-L-甲硫氨酸（SAM）是自由基SAM酶超家族中的中心辅因子，负责初级和次级代谢中的大量转化。在几乎所有的这些反应中，SAM的还原裂解被认为产生了一种活性物质，5′-脱氧腺苷自由基，它启动了催化作用。虽然在许多情况下的机制细节是很好理解的，但SAM的还原裂解仍然难以捉摸。在这份手稿中，我们已经测量了SAM的溶液峰电位为1.4 V（v SHE），并表明在控制电位条件下，它经历了不可逆的断裂为5′-脱氧腺苷自由基。虽然没有直接观察到自由基中间体，但通过形成8，5 ′-环腺苷和通过从溶剂可交换位点将H原子掺入5′-脱氧腺苷来推断其作为初始中间体的存在。类似地，在电解条件下也观察到2-氨基丁酸。这些结果的背景下，自由基SAM酶的SAM的还原裂解的影响进行了讨论。
S-Adenosyl-l-methionine (SAM) is the central cofactor in the radical SAM enzyme superfamily, responsible for a vast number of transformations in primary and secondary metabolism. In nearly all of these reactions, the reductive cleavage of SAM is proposed to produce a reactive species, 5′-deoxyadenosyl radical, which initiates catalysis. While the mechanistic details in many cases are well-understood, the reductive cleavage of SAM remains elusive. In this manuscript, we have measured the solution peak potential of SAM to be ∼−1.4 V (v SHE) and show that under controlled potential conditions, it undergoes irreversible fragmentation to the 5′-deoxyadenosyl radical. While the radical intermediate is not directly observed, its presence as an initial intermediate is inferred by the formation of 8,5′-cycloadenosine and by H atom incorporation into 5′-deoxyadenosine from solvent exchangeable site. Similarly, 2-aminobutyrate is also observed under electrolysis conditions. The implications of these results in the context of the reductive cleavage of SAM by radical SAM enzymes are discussed.