Crystal Structures of Drug-Metabolizing CYPs.
Crystal Structures of Drug-Metabolizing CYPs.
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DOI：
10.1007/978-1-0716-1554-6_7
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发表时间：
2021
影响因子：
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通讯作者：
D. F. Estrada;Amit Kumar;C. Campomizzi;N. Jay
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文献类型：
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作者：
D. F. Estrada;Amit Kumar;C. Campomizzi;N. Jay
药物代谢细胞色素P450酶（CYP）显示的复杂酶动力学（见第二章 9 ）可以部分地通过检查它们的晶体蛋白质结构来解释。幸运的是，尽管药物代谢CYP的不同家族之间的序列相似性较低，但在超家族内存在高度的结构同源性。蛋白质折叠的这种相似性允许直接比较CYP的结构特征，这些结构特征有助于底物结合、异嗜性和同嗜性协同性以及药物代谢中的遗传变异性的差异。在这一章中，我们首先提供了一个概述的命名和结构特征的作用，是共同的所有CYP。然后，我们应用这些定义来了解不同的底物特异性和功能的CYP3A，CYP2C和CYP2D酶家族。
The complex enzyme kinetics displayed by drug-metabolizing cytochrome P450 enzymes (CYPs) (seeChapter 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.