通过域互换和活性位点突变对三种双功能基合成和产品配置的结构洞察
Zhenyu Lei1, Ruiqing Lyu2, Wenlong Song1
1State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, China.
Journal of the American Chemical Society
|January 23, 2026
概括
研究人员发现了双功能合成酶 (TSs) 的新结构, 这些发现揭示了新的结构和酶功能,有助于设计新的分子.
科学领域:
- 生物化学
- 结构生物学
- 酵素学
背景情况:
- 合成酶 (TSs) 从多二酸盐中产生多样化的碳化合物骨.
- 一些TS具有双功能,具有前转移酶 (PT) 和旋酶 (TC) 域.
- 在本研究之前,对双功能PT-TC合成酶 (StTSs) 没有结构数据.
研究的目的:
- 确定三个全长的StTS的冷电磁结构.
- 研究PT-TC相互作用的结构基础及其对基生物合成的影响.
- 探索StTS的催化功能和结构多样性.
主要方法:
- 用于全长StTS结构的冷电子显微镜 (冷EM).
- 对于EvAS的TC域的X射线晶体学.
- 域互换实验和定位突变发生.
主要成果:
- 揭示了EVAS,EVSS和PbSS的独特PT驱动的六体化架构.
- EvSS具有独特的PT-六合体堆叠螺旋式空心管架构.
- 域名交换证明了PT对TC产品产量和类型的影响.
- 在EVAS TC域中确定了影响循环化的关键次要结构.
- 通过活性位子突变生成了七种新的基化合物.
结论:
- 发现了双功能StTS的新型结构架构.
- 扩大了对生物合成中的基质转移和催化机制的理解.
- 提供了PT-TC对用于生成的理性工程的见解.
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