在细胞染色体p450中以质子辅助的氧-氧键分裂
André R Groenhof1, Andreas W Ehlers, Koop Lammertsma
1Vrije Universiteit, FEW, Department of Chemistry, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands.
Journal of the American Chemical Society
|April 20, 2007
概括
质子化影响了细胞染色体P450水氧化合物0.0中的O-O键分裂. 这种质子转移调节了转化为铁氧化合物I的过程,影响了氧化途径.
科学领域:
- 生物化学 生物化学
- 计算化学计算化学
- 酶的机制 酶的机制
背景情况:
- 细胞染色体P450是参与各种代谢过程的关键酶.
- 了解催化循环,特别是O-O键裂解步骤,是阐明它们功能的关键.
- 水氧化合物0是P450催化循环中的关键中间体.
研究的目的:
- 为了研究细胞染色体P450水氧化合物0.0中以质子辅助的O-O键分裂的机制.
- 为了确定化合物0到化合物I转换的能量障碍和热力学有利性.
- 探索质子化在P450催化循环中的调节作用.
主要方法:
- 用密度函数理论 (DFT) 的计算来建模反应路径.
- 这项研究分析了质子源酸度对O-O键裂变屏障的影响.
- 研究了近接铁血红配体质子对反应能量学的影响.
主要成果:
- 确定了一个计算障碍,用于从0.0化合物中形成铁氧化合物I.
- 随着远端质子源变得不那么酸性,O-O键分裂屏障和内热度增加.
- 靠近铁的海姆配体的质子化促进了O-O键裂变.
- 在过氧化酶和酶模型中,化合物0转化为化合物I的转化略有外热.
结论:
- 质子转移在P450s中调节O-O键裂变方面发挥着至关重要的作用.
- 质子源的酸度和血配体的质子化是控制催化循环的重要因素.
- 化合物0和化合物I之间的能量关系会影响潜在的氧化途径.
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