The Atypical Cobalamin-Dependent S-Adenosyl-l-Methionine Nonradical Methylase TsrM and Its Radical Counterparts.
The Atypical Cobalamin-Dependent S-Adenosyl-l-Methionine Nonradical Methylase TsrM and Its Radical Counterparts.
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DOI：
10.1021/jacs.1c12064
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发表时间：
2022-04-06
影响因子：
15
通讯作者：
Drennan CL
中科院分区：
文献类型：
--
作者：
Ulrich EC;Drennan CL
钴胺素（Cbl）依赖性S-腺苷-L-甲硫氨酸（SNAMet）自由基甲基化酶因其使用双辅因子系统在未活性碳和磷中心进行挑战性的自由基甲基化反应而已知。这些酶是Cbl依赖性的C3 Met自由基酶的较大亚组的一部分，其也执行困难的环收缩和自由基重排。这个亚组是一个很大程度上未开发的不同化学的水库，需要在生化和结构表征，以揭示其复杂性的稳定努力。在这个角度来看，我们强调了多年来的重大努力，以阐明TsrM，意想不到的非自由基甲基化酶在这个亚组的功能，机制和结构。我们还讨论了最近在表征自由基甲基化酶亚组成员方面取得的成就，这些成就表明了机械酶学中的关键工具一次又一次地具有价值。最后，我们确定了最近的酶活性研究，利用生物信息学分析，以扩大我们的定义的亚组。毫无疑问，在自由基（和非自由基）酶化学和挑战性的转变，从这个亚组的未开发的空间的其他突破是在地平线上。
Cobalamin (Cbl)-dependent S-adenosyl-l-methionine (AdoMet) radical methylases are known for their use of a dual cofactor system to perform challenging radical methylation reactions at unactivated carbon and phosphorus centers. These enzymes are part of a larger subgroup of Cbl-dependent AdoMet radical enzymes that also perform difficult ring contractions and radical rearrangements. This subgroup is a largely untapped reservoir of diverse chemistry that requires steady efforts in biochemical and structural characterization to reveal its complexity. In this Perspective, we highlight the significant efforts over many years to elucidate the function, mechanism, and structure of TsrM, an unexpected nonradical methylase in this subgroup. We also discuss recent achievements in characterizing radical methylase subgroup members that exemplify how key tools in mechanistic enzymology are valuable time and again. Finally, we identify recent enzyme activity studies that have made use of bioinformatic analyses to expand our definition of the subgroup. Additional breakthroughs in radical (and nonradical) enzymatic chemistry and challenging transformations from the unexplored space of this subgroup are undoubtedly on the horizon.
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影响因子：
15
作者：
Byer AS;Yang H;McDaniel EC;Kathiresan V;Impano S;Pagnier A;Watts H;Denler C;Vagstad AL;Piel J;Duschene KS;Shepard EM;Shields TP;Scott LG;Lilla EA;Yokoyama K;Broderick WE;Hoffman BM;Broderick JB
通讯作者：
Broderick JB
影响因子：
4.6
作者：
Deobald D;Adrian L;Schöne C;Rother M;Layer G
通讯作者：
Layer G
影响因子：
56.9
作者：
DRENNAN, CL;HUANG, S;LUDWIG, ML
通讯作者：
LUDWIG, ML
影响因子：
2.9
作者：
BANERJEE, RV;FRASCA, V;MATTHEWS, RG
通讯作者：
MATTHEWS, RG
影响因子：
15
作者：
Blaszczyk, Anthony J.;Silakov, Alexey;Booker, Squire J.
通讯作者：
Booker, Squire J.