结构性洞察力 酸的生物合成中的酸结合形成
Tyler L Grove1, Paul M Himes2, Sungwon Hwang2
1Department of Biochemistry, Albert Einstein College of Medicine , Bronx, New York 10461, United States.
Journal of the American Chemical Society
|July 14, 2017
概括
这项研究揭示了CteB的结构,它是sactionipeptide生物合成中的关键酶. 了解这种结构可以揭示抗生素中形成必需的乙烯键的激素SAM酶机制.
科学领域:
- 生物化学
- 结构生物学
- 微生物学
背景情况:
- 赛克类是需要转化后桥 (赛克结) 的抗生素.
- 这种独特的结合是由使用基基化学和多个 [4Fe-4S] 集群的激素 SAM 酶形成的.
研究的目的:
- 为了确定sactionine键形成酶CteB的高分辨率晶体结构.
- 阐明松键形成的结构基础及其域的作用.
主要方法:
- 使用X射线结晶学来获得CteB的结构.
- 该结构以2.04 Å分辨率解决,并与SAM和基板片段共同结晶.
主要成果:
- 结构显示CteB具有 (β/α) 6-TIM桶折叠和一个具有两个 [4Fe-4S] 集群的C终端SPASM域.
- 一个关键的发现是SPASM域中的辅助 [4Fe-4S] 集群,具有动态协调站点.
- 一个类似于RiPP前体识别元素 (RRE) 的N终端域被确定.
结论:
- 这是第一种素结合酶的晶体结构, 提供了对激进SAM酶机制的关键见解.
- 该结构解释了CteB如何利用其 [4Fe-4S] 集群和基质结合部位来催化二结合的形成.
- 这些发现将有助于了解相关的酶,如Alba和ThnB,并有可能设计新型抗生素.
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