在二甲胺生物合成中使用非传统的激素S-甲胺酶选择基质依赖的裂变部位
Min Dong1, Masaki Horitani2,3, Boris Dzikovski1
1Department of Chemistry and Chemical Biology, Cornell University , Ithaca, New York 14853, United States.
Journal of the American Chemical Society
|April 7, 2017
概括
根性SAM酶可以在S-Adenosylmethionine (SAM) 类似物中切割不同的键. 这项研究表明, [4Fe-4S] 集群可以切换反应性,证明了多功能铁硫集群化学.
科学领域:
- 生物化学
- 酵素学
- 生物有机化学
背景情况:
- 激素S-腺胺 (SAM) 酶通常使用 [4Fe-4S] 集群将SAM的C5',腺胺-S键裂开以产生5'-脱氧腺胺基.
- 一些激进的SAM酶,如二胺生物合成中的酶,可以切割甲素的Cγ,Met-S键.
- 激素SAM酶的分裂机制和基质特异性是研究的关键领域.
研究的目的:
- 调查激素SAM酶是否可以被设计为SAM或其类型中的替代C-S键.
- 探索 [4Fe-4S] 集群在介导新型键裂解反应中的作用.
- 为了证明酶反应机制的基质依赖切换.
主要方法:
- 作为Pyrococcus horikoshii Dph2 (PhDph2) 酶的基质,使用了二氧化碳 SAM 模拟物 (dc-SAM).
- 使用电子核双共振 (ENDOR) 和质谱来描述反应中间体和产物.
- 研究了甲基裂变活性对4Fe-4S+集群的依赖性.
主要成果:
- PhDph2分裂了dc-SAM的C甲基-S键,形成了5'-deoxy-5'-(3-aminopropylthio) 腺 (dAPTA).
- 这种甲基分裂活动取决于4Fe-4S+集群.
- 观察到一种EPR活性中间体,表明 [4Fe-4S] 集群捕获甲基并将其转移到核友.
结论:
- 根性SAM酶可以通过改变SAM模拟结构来调整到与硫的三种C-S键中的任何一个.
- 这项研究首次证实了激素SAM酶从基于Fe的单电子转移转换为基于基质的基于S的双电子转移机制.
- 在酶催化中证明铁硫的多功能反应性.
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