A Radically Different Mechanism for S-Adenosylmethionine-Dependent Methyltransferases
A Radically Different Mechanism for S-Adenosylmethionine-Dependent Methyltransferases
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DOI：
10.1126/science.1200877
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发表时间：
2011-04-29
期刊：
影响因子：
56.9
通讯作者：
Booker, Squire J.
中科院分区：
文献类型：
--
作者：
Grove, Tyler L.;Benner, Jack S.;Booker, Squire J.
小分子和大分子的甲基化在代谢、细胞信号传导和表观遗传编程中至关重要，通常由s -腺苷甲硫氨酸（SAM）依赖的甲基转移酶实现。大多数SAM酶采用S(N)2机制将其底物上的亲核位点甲基化，但最近，已经发现自由基SAM酶可以通过5'-脱氧腺苷基5'-自由基的中间作用将不亲核的碳原子甲基化。我们已经确定了两个针对23S核糖体RNA中腺苷2503第2位和第8位sp(2)杂化碳的反应机制，分别由RlmN和Cfr催化。在这两种情况下，甲基都不会直接从SAM转移到RNA上；相反，这两种反应都是通过乒乓机制进行的，涉及保守的半胱氨酸残基的中间甲基化。
Methylation of small molecules and macromolecules is crucial in metabolism, cell signaling, and epigenetic programming and is most often achieved by S-adenosylmethionine (SAM)-dependent methyltransferases. Most employ an S(N)2 mechanism to methylate nucleophilic sites on their substrates, but recently, radical SAM enzymes have been identified that methylate carbon atoms that are not inherently nucleophilic via the intermediacy of a 5'-deoxyadenosyl 5'-radical. We have determined the mechanisms of two such reactions targeting the sp(2)-hybridized carbons at positions 2 and 8 of adenosine 2503 in 23S ribosomal RNA, catalyzed by RlmN and Cfr, respectively. In neither case is a methyl group transferred directly from SAM to the RNA; rather, both reactions proceed by a ping-pong mechanism involving intermediate methylation of a conserved cysteine residue.