Miles C S, Ost T W, Noble M A, Munro A W, Chapman S K
Institute of Cell and Molecular Biology, University of Edinburgh, Mayfield Road, Edinburgh EH9 3JR, UK.
Biochim Biophys Acta. 2000 Dec 29;1543(2):383-407. doi: 10.1016/s0167-4838(00)00236-3.
The cytochromes P-450 are an immensely important superfamily of heme-containing enzymes. They catalyze the monooxygenation of an enormous range of substrates. In bacteria, cytochromes P-450 are known to catalyze the hydroxylation of environmentally significant substrates such as camphor, phenolic compounds and many herbicides. In eukaryotes, these enzymes perform key roles in the synthesis and interconversion of steroids, while in mammals hepatic cytochromes P-450 are vital for the detoxification of many drugs. As such, the cytochromes P-450 are of considerable interest in medicine and biotechnology and are obvious targets for protein engineering. The purpose of this article is to illustrate the ways in which protein engineering has been used to investigate and modify the properties of cytochromes P-450. Illustrative examples include: the manipulation of substrate selectivity and regiospecificity, the alteration of membrane binding properties, and probing the route of electron transfer.
细胞色素P - 450是一个极其重要的含血红素酶的超家族。它们催化种类繁多的底物的单加氧反应。在细菌中，已知细胞色素P - 450催化对环境有重要意义的底物的羟基化反应，如樟脑、酚类化合物和许多除草剂。在真核生物中，这些酶在类固醇的合成和相互转化中起关键作用，而在哺乳动物中，肝细胞色素P - 450对许多药物的解毒至关重要。因此，细胞色素P - 450在医学和生物技术领域备受关注，是蛋白质工程的明显目标。本文的目的是阐述蛋白质工程用于研究和改变细胞色素P - 450性质的方式。实例包括：底物选择性和区域特异性的操纵、膜结合特性的改变以及对电子传递途径的探究。
