Bioelectronic delivery of electrons to cytochrome P450 enzymes.
Bioelectronic delivery of electrons to cytochrome P450 enzymes.
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DOI：
10.1021/jp201235m
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发表时间：
2011-07-07
影响因子：
3.3
通讯作者：
Rusling, James F.
中科院分区：
文献类型：
--
作者：
Krishnan, Sadagopan;Schenkman, John B.;Rusling, James F.
细胞色素p4500s （cyt p4500s）是人体药物和外源化学物质氧化代谢的主要氧化酶。在自然界中，铁血红素cyt p450利用还原酶从NADPH传递的氧和电子来立体和区域选择性地氧化底物。重要的研究已经指向实现这些事件的电化学。本文讨论了cyt p450薄膜的直接电化学性质，以及该薄膜在电化学驱动生物催化中的应用。维持和确认膜中cyt p450的结构完整性和催化活性是这些努力的基本特征。我们在这里强调了我们的努力，阐明铁血红素自旋状态和二级结构对人类细胞p450对伏安和生物催化性能的影响，使用方法定量描述薄膜中这些过程的动力学。我们还描述了第一个准确模拟自然生物催化途径的cyt P450/还原酶膜，并展示了如何将它们与伏安法一起使用来阐明关键的机制特征。这种生物电子cyt P450系统在未来的药物开发、毒性筛选、基础研究和化学合成系统中具有很高的价值。
Cytochrome P450s (cyt P450s) are the major oxidative enzymes in human oxidative metabolism of drugs and xenobiotic chemicals. In nature, the iron heme cyt P450s utilize oxygen and electrons delivered from NADPH by a reductase enzyme to oxidize substrates stereo- and regioselectively. Significant research has been directed toward achieving these events electrochemically. This feature article discusses the direct electrochemistry of cyt P450s in thin films, and the utilization of such films for electrochemically-driven biocatalysis. Maintaining and confirming structural integrity and catalytic activity of cyt P450s in films is an essential feature of these efforts. We highlight here our efforts to elucidate the influence of iron heme spin state and secondary structure of human cyt P450s on voltammetric and biocatalytic properties, using methodologies to quantitatively describe the dynamics of these processes in thin films. We also describe the first cyt P450/reductase films that accurately mimic the natural biocatalytic pathway, and show how they can be used with voltammetry to elucidate key mechanistic features. Such bioelectronic cyt P450 systems have high value for future drug development, toxicity screening, fundamental investigations, and chemical synthesis systems.
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