从结合到催化:一种原始酶的出现,赋予了内在的抗生素耐药性
Claudèle Lemay-St-Denis1,2,3,4, Stella Cellier-Goetghebeur1,2,3, Maxime St-Aubin1,2,3
1PROTEO, The Québec Network for Research on Protein, Function, Engineering and Applications, Québec, Canada.
Molecular biology and evolution
|September 19, 2025
概括
酶活性可以从结合蛋白的自我组装中出现. 乙型二叶酸还原酶 (DfrB) 通过同位四聚化进化初级催化,独立于抗生素耐药性.
科学领域:
- 酶学 是一种酶学.
- 进化生物学 进化生物学
- 结构生物学 结构生物学
背景情况:
- B型二叶酸还原酶 (DfrB) 与FolA酶不同,与抗生素耐药性有关.
- DfrB酶利用Src同质性3 (SH3) 折叠,通常是一种蛋白质结合模块,未知用于催化.
- 了解DfrB提供了对非催化蛋白域酶活性出现的见解.
研究的目的:
- 调查DfrB.中的酶活性的进化起源.
- 阐明DfrB结构,同质四聚化和催化功能的关系.
- 为了确定DfrB是否在应对抗生素压力时进化了其催化能力.
主要方法:
- 对DfrB同类物进行比较分析,以追踪进化保护.
- 实验和计算方法研究酶结构-功能关系.
- 评估同质四聚化对基质结合和催化物的影响.
主要成果:
- 在具有催化活性的DfrB同类物中没有保留活性部位残留物.
- DfrB的同质四聚化形成了一个具有正静电潜力的道,与催化活性有很强的相关性.
- DfrB的催化活性与它所赋予的抗生素耐药性无关,这表明它具有先前存在的能力.
结论:
- 在DfrB中的催化活性是从一个祖先的结合域的同质四化中产生的.
- DfrB的演变表明了初始的催化剂如何在机会上出现.
- 致病性细菌最近已经招募了这些进化的DfrB酶来抗生素耐药性.
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