一个乱伦的rSAM酶使多种交叉链接成为可能
Karsten A S Eastman1, Marcus C Mifflin1, Paul F Oblad1
1Department of Chemistry, University of Utah, 315 S. 1400 E, Salt Lake City, Utah 84112, United States.
ACS bio & med chem Au
|December 25, 2023
概括
在RiPP中形成乙烯交叉链的酶PapB显示出显著的基质灵活性. 它有效地修改了带有改变残留的,揭示了其活性位点和疗法的潜力.
科学领域:
- 生物化学 生物化学
- 酶学 是一种酶学.
- 自然产品 化学 化学
背景情况:
- 核糖体产生的和翻译后修饰的多 (RiPPs) 是一类多样化的自然产品.
- 激素S-adenosyl-l-methionine (rSAM) 酶PapB在PapA RiPP中催化和酸盐残留物之间的乙烯交叉链接.
研究的目的:
- 为了研究PapB酶的基质耐受性和特异性.
- 通过PapB.阐明乙烯交叉链形成的机制.
- 探索PapB作为治疗开发工具的潜力.
主要方法:
- 使用改性基质的酶分析.
- 合成带有改变侧链和配置的二聚体基质.
- 反应产品和酶动态的分析.
主要成果:
- PapB对含有硫醇和碳酸盐的残留物变异具有很高的耐受性,包括侧链延长和用四醇替换.
- 该酶有效地与重或充电的残留物,包括非天然的D-氨基酸进行交叉链接.
- 在原子抽象中,PapB表现出 diastereospecificity,并且可以促进脱氧腺基向脱基酸盐基质添加,表明产品抑制.
结论:
- 帕普B具有不寻常的乱交性,可以接受广泛的基质.
- 这项研究提供了对PapB.活体部位动态的关键见解.
- 帕普B的多功能性表明它在设计和开发新型治疗中具有潜在的实用性.
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