Protein engineering of cytochromes P-450

Caroline S Miles, Tobias W B Ost, Michael A Noble, Andrew W Munro, Stephen K Chapman

    Research output: Contribution to journalLiterature review

    58 Citations (Scopus)

    Abstract

    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 ill 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. (C) 2000 Elsevier Science B.V. All rights reserved.

    Original languageEnglish
    Pages (from-to)383-407
    Number of pages25
    JournalBiochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology
    Volume1543
    Issue number2
    DOIs
    Publication statusPublished - 29 Dec 2000

    Keywords

    • ESCHERICHIA-COLI
    • substrate specificity
    • HUMAN-LIVER
    • protein engineering
    • ACTIVE FUSION PROTEINS
    • electron transfer
    • SITE-DIRECTED MUTAGENESIS
    • chimeragenesis
    • genetic fusion
    • P-450
    • 3 KEY RESIDUES
    • CRYSTAL-STRUCTURE
    • NADPH-P450 REDUCTASE
    • ELECTRON-TRANSFER COMPLEX
    • P450 REDUCTASE
    • FATTY-ACID SUBSTRATE

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