Radical SAM-mediated methylation reactions.
Radical SAM-mediated methylation reactions.
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DOI：
10.1016/j.cbpa.2013.05.032
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发表时间：
2013-08
影响因子：
7.8
通讯作者：
Fujimori, Danica Galonic
中科院分区：
文献类型：
--
作者：
Fujimori, Danica Galonic
属于自由基S-腺苷甲硫氨酸（SAM）超家族的酶的子集能够催化甲基化反应。这些酶的底物不同于通过极性机制进行甲基化的亲核底物。最近，几种自由基SAM甲基化酶的活性已经在体外重建，并研究了它们的催化机制。RNA修饰酶RlmN和Cfr通过甲基合酶机制催化甲基化。这些酶以两种不同的角色使用SAM：作为甲基转移到保守半胱氨酸的来源和作为5′-脱氧腺苷自由基（5′-dA·）的来源。通过这种物质夺取氢原子产生硫代亚甲基自由基，其加入RNA底物中，形成酶-底物共价加合物。在最近的另一项研究中，自由基SAM和钴胺素结合结构域酶TsrM对色氨酸吲哚部分的甲基化已经被重建。甲钴胺在TsrM中充当中间甲基供体，并且被提议将甲基基团作为甲基自由基转移。有趣的是，尽管存在自由基SAM基序，但在这种甲基化中没有观察到SAM的还原裂解。这些重要的重组为进一步研究自由基甲基化的机制奠定了基础。
A subset of enzymes that belong to the radical S-adenosylmethionine (SAM) superfamily are able to catalyze methylation reactions. Substrates of these enzymes are distinct from the nucleophilic substrates that undergo methylation by a polar mechanism. Recently, activities of several radical SAM methylating enzymes have been reconstituted in vitro and their mechanisms of catalysis investigated. The RNA modifying enzymes RlmN and Cfr catalyze methylation via a methyl synthase mechanism. These enzymes use SAM in two distinct roles: as a source of a methyl group transferred to a conserved cysteine and as a source of 5′-deoxyadenosyl radical (5′-dA•). Hydrogen atom abstraction by this species generates a thiomethylene radical which adds into the RNA substrate, forming an enzyme-substrate covalent adduct. In another recent study, methylation of the indole moiety of tryptophan by the radical SAM and cobalamin-binding domain enzyme TsrM has been reconstituted. Methylcobalamin serves as an intermediate methyl donor in TsrM, and is proposed to transfer the methyl group as a methyl radical. Interestingly, despite the presence of the radical SAM motif, no reductive cleavage of SAM has been observed in this methylation. These important reconstitutions set the stage for further studies on mechanisms of radical methylation.
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自由基 SAM 酶进行甲基转移的结构基础。
DOI：
10.1126/science.1205358
发表时间：
2011-05-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Boal AK;Grove TL;McLaughlin MI;Yennawar NH;Booker SJ;Rosenzweig AC
通讯作者：
Rosenzweig AC
影响因子：
6.8
作者：
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通讯作者：
Datta, Supratim
影响因子：
3.3
作者：
Kudo, Furnitaka;Kasama, Yuko;Eguchi, Tadashi
通讯作者：
Eguchi, Tadashi
影响因子：
14.9
作者：
Kaminska KH;Purta E;Hansen LH;Bujnicki JM;Vester B;Long KS
通讯作者：
Long KS
DOI：
10.1073/pnas.0708608105
发表时间：
2008-02-12
影响因子：
11.1
作者：
Anton, Brian P.;Saleh, Lana;Roberts, Richard J.
通讯作者：
Roberts, Richard J.