Mechanisms of cytochrome p450 substrate oxidation: MiniReview
Mechanisms of cytochrome p450 substrate oxidation: MiniReview
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DOI：
10.1002/jbt.20174
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发表时间：
2007-01-01
影响因子：
3.6
通讯作者：
Guengerich, F. Peter
中科院分区：
文献类型：
--
作者：
Guengerich, F. Peter
细胞色素P450(P450)酶催化多种氧化和还原反应，涉及数千种底物。一般的化学机制可以用来使大多数氧化反应合理化，包括二芳基中间体(FeO_3+)和奇电子化学，即氢原子或电子的抽离，随后是氧的反弹和有时的重排。这一一般机理可以解释碳羟化、杂多酚氧化和脱烷基化、环氧化、脱饱和、血红素破坏等反应。另一种理解催化的方法涉及分析更一般的催化循环，包括底物特异性，因为用几个P450观察到复杂的协作性模式。一些复杂性是由于蛋白质在与其他步骤相同的时间尺度上发生的缓慢构象变化。
Cytochrome P450 (P450) enzymes catalyze a variety of oxidation and some reduction reactions, collectively involving thousands of substrates. A general chemical mechanism can be used to rationalize most of the oxidations and involves a perfenyl intermediate (FeO3+) and odd-electron chemistry, i.e. abstraction of a hydrogen atom or electron followed by oxygen rebound and sometimes rearrangement. This general mechanism can explain carbon hydroxylation, heteroatorn oxygenation and dealkylation, epoxidation, desaturation, heme destruction, and other reactions. Another approach to understanding catalysis involves analysis of the more general catalytic cycle, including substrate specificity, because complex patterns of cooperativity are observed with several P450s. Some of the complexity is due to slow conformational changes in the proteins that occur on the same timescale as other steps.