在α/β-水解酶折叠处从水解性到氧解性催化物的进化适应
Soi Bui1, Sara Gil-Guerrero2, Peter van der Linden3
1Randall Centre for Cell and Molecular Biophysics, King's College London London SE1 1UL UK roberto.steiner@kcl.ac.uk.
Chemical science
|October 6, 2023
概括
进化重新定位的α/β-酶 (ABH) 折叠酶用于氧化. 这项研究揭示了1-H-3-hydroxy-4-oxoquinaldine 2,4-dioxygenase (HOD) 如何使用其活性位点来结合和激活新型反应中的二氧化物.
科学领域:
- 生物化学 生物化学
- 进化生物学 进化生物学
- 结构生物学 结构生物学
背景情况:
- 蛋白质折叠适应是进化新酶功能的关键.
- 阿尔法/β-酶 (ABH) 折叠酶通常不会进行氧化.
- 降解N-异芳基质的辅因子独立氧化酶利用ABH折叠.
研究的目的:
- 研究ABH折叠超级家族内的辅因子独立氧化酶的机制.
- 阐明原型的1-H-3-hydroxy-4-oxoquinaldine 2,4-dioxygenase (HOD) 如何催化氧化反应.
- 了解ABH折叠的进化重用,以获得新的酶活性.
主要方法:
- 在正常和高氧条件下进行综合晶体分析.
- 分子动力学和量子力学计算.
- 结陷加压,以确定三元复杂结构.
主要成果:
- 二氧化物 (O2) 定位到活性位点的"氧化离子孔"是由"核友肘"残留物调节的.
- 一个疏水口袋就像一个近邻的O2储一样.
- O2方向与基板电荷相结合,基板deprotonation旋转O2以实现最佳的电荷转移和过氧化物中间形成.
结论:
- 进化成功地重新利用了ABH折叠架构,用于金属独立氧化.
- HOD的催化机制使N-异芳基质的辅因子独立氧化成为可能.
- 提供了关于基质激活和O2激活的详细机制见解.
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