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Crystal Structures of Drug-Metabolizing CYPs

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Enzyme Kinetics in Drug Metabolism

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2342))

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Abstract

The complex enzyme kinetics displayed by drug-metabolizing cytochrome P450 enzymes (CYPs) (see Chapter 9) can, in part, be explained by an examination of their crystallographic protein structures. Fortunately, despite low sequence similarity between different families of drug-metabolizing CYPs, there exists a high degree of structural homology within the superfamily. This similarity in the protein fold allows for a direct comparison of the structural features of CYPs that contribute toward differences in substrate binding, heterotropic and homotropic cooperativity, and genetic variability in drug metabolism. In this chapter, we first provide an overview of the nomenclature and the role of structural features that are common in all CYPs. We then apply these definitions to understand the different substrate specificities and functions in the CYP3A, CYP2C, and CYP2D families of enzymes.

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Authors and Affiliations

  1. Department of Biochemistry, University at Buffalo, Buffalo, NY, USA

    D. Fernando Estrada, Amit Kumar, Christopher S. Campomizzi & Natalie Jay

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  1. D. Fernando Estrada
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  2. Amit Kumar
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  3. Christopher S. Campomizzi
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  4. Natalie Jay
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Correspondence to D. Fernando Estrada .

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  1. Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA, USA

    Swati Nagar

  2. Translational Medicine, Novartis Institutes for Biomedical Research, Inc., Cambridge, MA, USA

    Upendra A. Argikar

  3. Independent, Harleysville, PA, USA

    Donald Tweedie

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Estrada, D.F., Kumar, A., Campomizzi, C.S., Jay, N. (2021). Crystal Structures of Drug-Metabolizing CYPs. In: Nagar, S., Argikar, U.A., Tweedie, D. (eds) Enzyme Kinetics in Drug Metabolism. Methods in Molecular Biology, vol 2342. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1554-6_7

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