苏尔M的产生单巴克坦的铁酶域的结构与上游载体蛋白质域形成了一个独特的复合体
Ketan D Patel1, Ryan A Oliver2, Michael S Lichstrahl2
1Department of Structural Biology, University at Buffalo, SUNY, Buffalo, NY, 14203, USA.
bioRxiv : the preprint server for biology
|April 15, 2024
概括
非核糖体合成酶 (NRPSs) 使用组装线生产生物活性. 一个 thioesterase 域.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 分子生物学分子生物学
背景情况:
- 非核糖体合成酶 (NRPS) 是大型分子机器,可以合成多种生物活性.
- NRPS的功能是装配线,载体域在催化域之间连接和转移不断增长的链.
- 虽然大多数NRPS域执行标准化学,但有些表现出独特的催化活动,导致新的产品结构.
研究的目的:
- 阐明非同寻常的β-乳酸环形成的结构基础,这种形成由特定的NRPS硫酶域催化.
- 了解β-乳酸抗生素硫法泽生产的机制.
- 识别结构特征,使得能够发现新的β-乳糖生成基因集群.
主要方法:
- 使用X射线晶体学来确定硫酶域的三维结构.
- 对独立的铁酶域和具有基载体域的二域复合体进行了结构分析.
- 生物信息分析和基因组挖掘被用来识别相关的基因集群.
主要成果:
- 确定的结构揭示了在铁酶域内一个受约束的活性位点.
- 这种活性位点架构对于为特征性β-乳酸环闭合方向基质至关重要.
- 结构洞察力与在β-乳酸形成硫酶域中观察到的类似.
结论:
- 确定的结构为NRPS硫酶域的β-乳酸形成机制提供了关键的见解.
- 这项工作阐明了自然产品生物合成途径中不寻常的化学转变的结构基础.
- 这些发现可以识别新的NRPS相关基因集群,扩大NRPS衍生的天然产品已知的化学多样性.
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