可逆的基因素脱乙酶活性催化了氨酸化
Takeshi Tsusaka1, Mohd Altaf Najar2, Benjamin Schwarz3
1Department of Physiology, University of California, San Francisco, San Francisco, CA, USA.
Nature chemical biology
|March 27, 2025
概括
希斯脱乙酶 (HDACs) 意外地催化了蛋白质β-xybutyrylation (Kbhb),这是一个新的翻译后修饰. 这一发现通过一种新的可逆酶活性将能量代谢和蛋白质修饰联系在一起.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 代谢学 代谢学 代谢学
背景情况:
- 代谢物动态修改蛋白质,将能量代谢和翻译后修改 (PTMs) 联系起来.
- 饥饿和低碳水化合物饮食增加了β-基酸盐 (BHB) 和氨酸β-基基化 (Kbhb).
研究的目的:
- 为了研究氨酸β-氧基化 (Kbhb) 背后的酶机制.
- 探索基因组脱乙酶 (HDACs) 在催化Kbhb.中的作用.
主要方法:
- 第I类HDACs的突变分析.
- 生物化学分析检测Kbhb的形成.
- 对酶活性部位残留物的分析.
主要成果:
- 一级HDACs意外催化Kbhb的形成.
- 关键的活性部位氨基酸对于脱乙基化和β-基基化都至关重要.
- HDACs催化 lysine 和 BHB 之间的凝结反应.
结论:
- HDACs具有一种新的,非正规的Beta-hydroxybutyrylation的酶活性.
- 这种可逆的PTM机制将代谢状态与蛋白质组修饰联系起来.
- 该活性扩展到其他短链脂肪酸,表明在PTM沉积中发挥了更广泛的作用.
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