循环甲基化的结构基础由一个可巴胺依赖的激素S-adenosylmethionine酶在cystobactamids生物合成
Jiayuan Cui1,2, Bo Wang1,2,3, Ravi K Maurya1,2
1Department of Chemistry, The Pennsylvania State University, University Park, PA, USA.
bioRxiv : the preprint server for biology
|December 3, 2025
概括
赛斯托巴克塔米德是抗菌性DNA旋转酶抑制剂. 一种依赖可巴胺的酶,CysS,通过使用激素S-adenosylmethionine (SAM) 进行反细菌功能,代甲基化基质.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 自然产品 化学 化学
背景情况:
- 赛斯托巴克塔米德是强大的抗菌剂,可以抑制DNA旋转酶.
- 它们在para-aminobenzoic酸部分上的独特的alkoxy组对活性至关重要.
- 这些修改是通过由CysS酶催化的代甲基化实现的.
研究的目的:
- 为了阐明可巴胺 (Cbl) 依存的激素S-adenosylmethionine (SAM) 酶CysS的机制.
- 了解CysS如何促进Cbl甲基化和代基质甲基化.
- 为CysS在甲基化过程中对基质和产品的容纳提供结构性见解.
主要方法:
- 在X射线晶体学.
- 来自Corallococcus sp.的CysS同类体的三个晶体结构的确定. CA054B. CA054B. 这是一个很好的例子.
- 在基质和连接物存在或不存在的情况下进行结构分析.
主要成果:
- 结构揭示了CysS在代甲基化过程中如何结合含有甲氧基和甲氧基的基质.
- 一个没有基质的结构显示了构造变化,使胺甲基化成为可能.
- 该酶利用乒乓球机制,每次甲基化周期消耗两个SAM分子.
结论:
- 结构数据提供了关于CysS在Cbl和基质甲基化中的双重作用的机制性见解.
- 了解CysS机制可以帮助开发新型抗菌剂.
- 代甲基化过程是产生多样化的囊泡胺结构的关键.
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