基因组数据库提供了一个功能II类甘氨酸-tRNA合成酶urzyme的自发例子
Sourav Kumar Patra1, Jordan Douglas2,3, Peter R Wills2
1Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599-7260.
bioRxiv : the preprint server for biology
|January 23, 2024
概括
研究人员从北极狐的DNA中设计了一种新的祖先酶GlyCA. 这种"酶"有效地激活了甘氨酸,支持了早期遗传代码进化理论的理论,其中包括减少的氨基酸字母表.
科学领域:
- 生物化学 生物化学
- 生命的起源研究 生命的起源研究
- 分子进化分子进化
背景情况:
- 研究遗传密码的起源受到古代氨基酸-tRNA合成酶 (AARS) 缺乏实验模型的阻碍.
- 现代AARS中保存的催化场所被假设代表这些祖先酶.
- 之前的工作成功地设计了来自TrpRS,LeuRS和HisRS的尿酶.
研究的目的:
- 来自北极狐基因的第四个urzyme,GlyCA的工程和特征.
- 调查GlyCA的催化活性和基质特异性.
- 评估酶在遗传密码的出现中的作用.
主要方法:
- 从*Vulpes lagopus*基因组数据中识别和表达了GlyCA的N端81氨基酸.
- 利用Alphafold2进行结构预测,将GlyCA与HisRS酶 (HisCA1) 进行比较.
- 进行了酶性表征,包括ATP消耗和tRNA氨基化的动态分析.
主要成果:
- 设计了一种具有高催化效率的功能性GlyCA尿酶,用于甘氨酸激活.
- 与HisCA1和全长GlyRS-B.相比,GlyCA显示了ATP消耗和甘氨酸激活的显著更高的速度.
- GlyCA优先激活II类氨基酸,补充了HisCA和LeuAC的特异性.
结论:
- 酶,就像新特征的GlyCA一样,具有对简化遗传密码至关重要的祖先催化活动.
- 这些发现支持了保留的酶核可以作为早期生物化学系统的模型的假设.
- GLYCA的特性为遗传密码和蛋白质合成的逐步演变提供了实验证据.
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