Mammalian microsomal cytochrome P450 monooxygenase: Structural adaptations for membrane binding and functional diversity
Mammalian microsomal cytochrome P450 monooxygenase: Structural adaptations for membrane binding and functional diversity
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DOI：
10.1016/s1097-2765(00)80408-6
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发表时间：
2000-01-01
期刊：
影响因子：
16
通讯作者：
McRee, DE
中科院分区：
文献类型：
--
作者：
Williams, PA;Cosme, J;McRee, DE
微粒体细胞色素P450参与异生物质解毒、原致癌物活化和类固醇激素合成。哺乳动物微粒体P450的第一个结构表明，P450与内质网的关联涉及由多肽链的非连续部分形成的蛋白质的疏水表面。这种相互作用将假定的底物进入通道的入口置于膜中或膜附近，并将邻近血红素辅因子的蛋白质的面定向为垂直于膜平面，以与P450还原酶相互作用。这种结构为其他哺乳动物P450的建模提供了模板，并有助于药物发现和药物相互作用的预测。
Microsomal cytochrome P450s participate in xenobiotic detoxification, procarcinogen activation, and steroid hormone synthesis. The first structure of a mammalian microsomal P450 suggests that the association of P450s with the endoplasmic reticulum involves a hydrophobic surface of the protein formed by noncontiguous portions of the polypeptide chain. This interaction places the entrance of the putative substrate access channel in or near the membrane and orients the face of the protein proximal to the heme cofactor perpendicular to the plane of the membrane for interaction with the P450 reductase. This structure offers a template for modeling other mammalian P450s and should aid drug discovery and the prediction of drug-drug interactions.