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Quantification of Coenzyme A in Cells and Tissues
Published on: September 27, 2019
如何在辅酶B12酶中分裂Co-C键:一个理论研究
1Department of Theoretical Chemistry, Lund University, Chemical Center, P.O. Box 124, S-221 00 Lund, Sweden.
Journal of the American Chemical Society
|June 23, 2005
概括
维生素B12酶极大地加速了Co-C键裂变. 这项研究揭示了蛋白质诱导的辅酶扭曲和稳定显著降低了键解离能,解释了酶的作用.
科学领域:
- 生物化学 生物化学
- 酶学 是一种酶学.
- 计算化学的计算化学
背景情况:
- 维生素B12依赖的酶催化了涉及对有机金属Co-C键的同解裂的反应.
- 蛋白质环境的催化加速与孤立的辅因子相比大约是1012倍.
- 了解这种显著的速率增强的机制仍然是酶学中的一个关键问题.
研究的目的:
- 阐明维生素B12依赖酶中增强的Co-C键裂变背后的分子机制.
- 量化酶活性部位内的各种因素对催化作用的贡献.
- 研究辅酶扭曲和静电相互作用在加速反应中的作用.
主要方法:
- 采用了量子力学和分子力学 (QM/MM) 组合的方法.
- 计算的重点是酶谷氨酸突变酶中的Co-C键裂变.
- 分析因蛋白相互作用而导致的键解离能 (BDE) 变化.
主要成果:
- 在酶内,腺索基可巴胺中Co-C键的计算BDE减少了135kJ/mol.
- 关键的贡献因素包括激素稳定 (20 kJ/mol),解离状态的静电/范德瓦尔斯稳定 (42 kJ/mol),蛋白质稳定 (11 kJ/mol) 和显著的辅酶几何扭曲 (61 kJ/mol).
- 同酶的变形,特别是核糖部分和Co-C5'-C4'角的变形,对于催化是至关重要的.
结论:
- 酶的活性部位通过静电,范德瓦尔斯和硬质效应的组合显著降低了Co-C键解离能.
- 蛋白质环境对辅酶的几何扭曲是催化加速的主要驱动因素.
- 极性核糖组在调解这些效应方面发挥着至关重要的作用,而非极性类似物显示出减少的催化增强.
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