Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA.
Biochemistry. 2011 Feb 1;50(4):440-2. doi: 10.1021/bi101255e. Epub 2011 Jan 5.
Activation of glycyl radical enzymes (GREs) by S-adenosylmethonine (AdoMet or SAM)-dependent enzymes has long been shown to proceed via the reductive cleavage of SAM. The AdoMet-dependent (or radical SAM) enzymes catalyze this reaction by using a [4Fe-4S] cluster to reductively cleave AdoMet to form a transient 5'-deoxyadenosyl radical and methionine. This radical is then transferred to the GRE, and methionine and 5'-deoxyadenosine are also formed. In contrast to this paradigm, we demonstrate that generation of a glycyl radical on the B(12)-independent glycerol dehydratase by the glycerol dehydratase activating enzyme results in formation of 5'-deoxy-5'-(methylthio)adenosine and not 5'-deoxyadenosine. This demonstrates for the first time that radical SAM activases are also capable of an alternative cleavage pathway for SAM.
甘氨酰自由基酶（GREs）的激活长期以来一直被证明是通过 S-腺苷甲硫氨酸（AdoMet 或 SAM）依赖性酶的还原裂解来进行的。AdoMet 依赖性（或自由基 SAM）酶通过使用 [4Fe-4S] 簇还原裂解 AdoMet 来催化该反应，形成瞬态 5'-脱氧腺苷自由基和蛋氨酸。然后，该自由基被转移到 GRE，同时也形成蛋氨酸和 5'-脱氧腺苷。与这一范式相反，我们证明甘油脱水酶激活酶在 B(12) 独立的甘油脱水酶上产生甘氨酰自由基，导致形成 5'-脱氧-5'-(甲硫基)腺苷，而不是 5'-脱氧腺苷。这首次证明了自由基 SAM 激活酶也能够进行 SAM 的替代裂解途径。
