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Crystal Structures of Drug-Metabolizing CYPs.

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.

SUBMITTER: Estrada DF

PROVIDER: S-EPMC10813703 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Crystal Structures of Drug-Metabolizing CYPs.

Estrada D Fernando DF Kumar Amit A Campomizzi Christopher S CS Jay Natalie N

Methods in molecular biology (Clifton, N.J.) 20210101

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 diff ...[more]

PMID: 34272695

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