蜂诺丁-2和诺丁:带有阿斯巴提胺后翻译修饰的拉索
Li Cao1, Moshe Beiser2, Joseph D Koos3
1Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey 08544, United States.
Journal of the American Chemical Society
|July 20, 2021
概括
蛋白质l-异甲基转移酶 (PIMT) 同类物通过形成刚性化阿斯巴提胺环来修改拉索. 这一发现揭示了PIMTs在拉索生物合成中的新后翻译修饰 (PTM) 功能.
科学领域:
- 生物化学
- 分子生物学
- 结构生物学
背景情况:
- 拉索是一种由核糖体合成和翻译后修饰的 (RiPPs),其特点是具有独特的线程结构和异键.
- 已经确定了其他翻译后修饰 (PTM),进一步多样化了拉索的结构和功能.
研究的目的:
- 研究与拉索生物合成基因集群 (BGCs) 相关的蛋白质l-异甲基转移酶 (PIMT) 同类的新型作用.
- 描述PIMT介导的变化对激光的机制和结构影响.
主要方法:
- 基因组挖掘以识别与PIMT同类同位的拉索BGC.
- 修饰的拉索 (cellulonodin-2和lihuanodin) 的异构表达和结构特征.
- 在实验室中制PIMT介导的阿斯巴提胺形成.
主要成果:
- 鉴定了与拉索BGC相关的PIMT同类物,表明一种新的PTM途径.
- 证明这些PIMT在拉索环内甲基化酸侧链,形成稳定的阿斯巴提胺.
- 与未经修改的同类药物相比,阿斯巴提胺修改的拉索具有更高的刚性.
- 观察到与拉索相关的PIMTs的快速甲基转移酶活性,特定于拉索基质.
结论:
- 蛋白质l-异甲基转移酶 (PIMTs) 在翻译后修改拉索中具有新功能,与它们已知的蛋白质修复作用不同.
- 在拉索环内由PIMT介导的阿斯巴提胺部分的形成增强了结构刚性.
- 这种PTM途径在多种生物中保持,突出显示了它在拉索多样化中的重要性.
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