School of Chemistry and ARC Centre of Excellence for Free Radical Chemistry and Biotechnology, University of Sydney, Sydney, NSW 2006, Australia.
J Am Chem Soc. 2012 Jan 25;134(3):1591-9. doi: 10.1021/ja207809b. Epub 2012 Jan 6.
Vitamin B(12) and its biologically active counterparts possess the only examples of carbon-cobalt bonds in living systems. The role of such motifs as radical reservoirs has potential application in future catalytic and electronic nanodevices. To fully understand radical generation in coenzyme B(12) (dAdoCbl)-dependent enzymes, however, major obstacles still need to be overcome. In this work, we have used Car-Parrinello molecular dynamics (CPMD) simulations, in a mixed quantum mechanics/molecular mechanics (QM/MM) framework, to investigate the initial stages of the methylmalonyl-CoA-mutase-catalyzed reaction. We demonstrate that the 5'-deoxyadenosyl radical (dAdo(•)) exists as a distinct entity in this reaction, consistent with the results of extensive experimental and some previous theoretical studies. We report free energy calculations and first-principles trajectories that help understand how B(12) enzymes catalyze coenzyme activation and control highly reactive radical intermediates.
维生素 B(12)及其生物活性类似物拥有生命系统中唯一的碳-钴键实例。此类自由基储库的作用在未来的催化和电子纳米器件中有潜在的应用。然而，要充分了解辅酶 B(12)(dAdoCbl)依赖性酶中的自由基生成，仍需要克服主要障碍。在这项工作中，我们使用 Car-Parrinello 分子动力学（CPMD）模拟，在混合量子力学/分子力学（QM/MM）框架中，研究了甲基丙二酰辅酶 A 变位酶催化反应的初始阶段。我们证明，在该反应中，5'-脱氧腺嘌呤核苷自由基（dAdo(•)）以独特的实体存在，这与广泛的实验和一些先前的理论研究结果一致。我们报告了自由能计算和第一性原理轨迹，有助于理解 B(12) 酶如何催化辅酶的激活并控制高反应性自由基中间体。
