一个C类激素的S-Adenosyl-l-methionine thiazole甲基转移酶的机制
Zhengan Zhang1,2, Nilkamal Mahanta1,3, Graham A Hudson1
1Department of Chemistry, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
Journal of the American Chemical Society
|December 1, 2017
概括
这项研究揭示了C级激素S- 腺甲 (rSAM) 甲基转移酶TbtI的机制,该激素对硫抗生素生物合成至关重要. 它揭示了一种新型的甲基化途径,
科学领域:
- 生物化学
- 有机化学
- 分子生物学
背景情况:
- 激进的S-adenosylmethionine (rSAM) 甲基转移酶催化非活性碳中心的甲基化.
- 已确定了四类rSAM甲基转移酶,但B-D类的机制在很大程度上仍未知.
- 了解这些机制对于阐明复杂的生物合成途径至关重要.
研究的目的:
- 研究CrSAM类甲基转移酶TbtI的详细机制.
- 阐明 TbtI 在硫抗生素 thiomuracin 的生物合成中的作用.
- 在翻译后成熟过程中描述Cys衍生的醇的甲基化.
主要方法:
- 通过TbtI介导的甲基化产品分析.
- 使用S-adenosylmethionine (SAM) 的同位素标记研究.
- 对转移路径和溶剂交换的分析.
主要成果:
- TbtI需要两个SAM分子来对提亚前体进行C-甲基化.
- 一个SAM转化为5'-脱氧腺,第二个转化为S-adenosyl-l-homocysteine (SAH).
- 从SAM2的甲基转移到SAM1并被纳入产品的明显转移,以及 thiazole β位置的转移.
结论:
- 为C类rSAM甲基转移酶提出了一种新的甲基化机制.
- 这种机制与其他表征的rSAM甲基转移酶有显著差异.
- 这些发现提供了关于硫抗生素生物合成的重要见解.
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