化学蛋白质学揭示了通过氧化后翻译性修饰来调节胆盐水解酶的作用
Amy K Bracken1, Kien P Malarney2, Pamela V Chang1,3,4,5,6
1Department of Chemistry and Chemical Biology, 162 Sciences Dr., Cornell University, Ithaca, NY 14853, United States.
bioRxiv : the preprint server for biology
|December 19, 2025
概括
肠道细菌通过胆盐酸酶 (BSH) 调节胆酸代谢. 我们发现,关键的氨酸残留物 (Cys2) 的可逆氧化使BSH失活,提供了一个新的调节机制.
科学领域:
- 微生物学 微生物学
- 生物化学 生物化学
- 酶学 是一种酶学.
背景情况:
- 肠道微生物组将胆酸代谢成信号分子.
- 胆盐化酶 (BSH) 对于这种胆酸生物转化至关重要.
- 对BSH活动的监管仍然不太了解.
研究的目的:
- 为了研究胆汁盐酸酶 (BSH) 活性的调节.
- 为了识别影响BSH功能的翻译后修改.
- 开发一种方法来分析肠道微生物群中的BSH修饰.
主要方法:
- 描述BSH活性部位的氨酸氧化状态.
- 开发一种硫酸-反应性胆酸探针.
- 在肠道微生物群中对BSH Cys2氧化进行化学蛋白质分析.
主要成果:
- 在BSH中的催化氨酸2 (Cys2) 可以存在于硫酸 (Cys-SOH) 状态.
- 这种可逆氧化 (oxPTM) 失活了BSH的催化活性.
- 一些肠道BSH酶通过Cys2氧化可逆性失活.
结论:
- BSH Cys2的可逆氧化是一种新的酶调节机制.
- 这种氧化状态调节BSH活动,以应对生理变化.
- BSH oxPTM 提供了对肠道微生物群胆酸代谢的洞察.
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