代谢在4亿年来形成酶结构中的作用
Oliver Lemke1,2, Benjamin Murray Heineike1,3,4, Sandra Viknander5
1Department of Biochemistry, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Nature
|July 9, 2025
概括
在数百万年的时间里,新陈代谢对蛋白质结构的演变产生了重大影响. 酶进化受到功能和代谢利基的限制, 不仅仅是成本优化.
科学领域:
- 进化生物学
- 结构生物学
- 生物化学
背景情况:
- 深度学习和AlphaFold2能够进行大规模的蛋白质结构预测.
- 蛋白质结构对于理解功能和进化至关重要.
研究的目的:
- 在Saccharomycotina研究了4亿年的新陈代谢进化.
- 将酶序列分离与代谢特性和结构演变联系起来.
主要方法:
- 分析了11269个预测和实验性酶结构.
- 通过225个途径检查了361个代谢反应.
- 保护区域的序列分离与代谢特性相关.
主要成果:
- 代谢在多个尺度上塑造了酶的结构演变.
- 酶进化受到反应机制,相互作用,流量和成本的限制.
- 层次模式显示表面残留物迅速演变,而结合点则被保留.
结论:
- 酶进化是由催化功能控制的,并由代谢利基,网络,成本和相互作用形成.
- 结构背景决定了氨基酸替代率.
- 小分子结合点在没有成本优化的情况下在选择性约束下演变.
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