伪基因酶可以通过 thioether 交叉连接催化循环.
Ling Hu1,2,3, Miao Li2,4, Yueqian Sang5
1School of Life Science & Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
Nature chemistry
|October 2, 2025
概括
伪基因酶,通常是不活跃的酶,意外地催化了酸环化,形成乙烯键. 这一发现揭示了蛋白激酶折叠在生物合成中的新功能.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 类似蛋白激酶的超级家族蛋白质对于通过酸化进行细胞信号传递至关重要.
- 伪激酶是缺乏正规激酶活性的相关蛋白质,其中一些具有独特的催化功能.
- 核糖体合成和翻译后修改的,如胺和兰氏,涉及复杂的修改.
研究的目的:
- 为了研究除了酸化之外的伪基因酶的酶活性.
- 识别和描述特定伪基因酶 (TvaE和SacE) 的旋活性.
- 探索由这些伪基因酶催化 (ene) 乙残留物形成的机制.
主要方法:
- 对 thioamitides 和 lanthipeptides 的生物合成研究.
- 伪基因酶的生物化学表征和异质表达.
- 同结晶,计算分析和特定位点的突变发生.
- 基因组挖掘和同位素标记研究.
主要成果:
- 发现伪基因酶TvaE和SacE具有循环活性,形成 (ene) thioether残留物.
- 该研究确定了在不和的2-aminovinyl-cysteine形成中的专用循环酶活性,并探索了和的氨酸形成.
- 阐明了一种常见的催化机制,涉及迈克尔添加用于交叉链接,与正规蛋白质激酶不同.
结论:
- 蛋白激酶折叠可以重新用于新的催化功能,例如循环.
- 伪基因酶可以充当循环酶,催化迈克尔的添加,用于 thioether 交叉连接.
- 这一发现扩大了已知的伪激酶和蛋白质激酶类蛋白质的功能表.
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