Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacký University Olomouc, tř. 17, listopadu 12, 771 46 Olomouc, Czech Republic.
Department of Pharmacology, Faculty of Medicine and Dentistry, Palacký University Olomouc, Hněvotínská 3, 775 15 Olomouc, Czech Republic.
J Inorg Biochem. 2018 Jun;183:117-136. doi: 10.1016/j.jinorgbio.2018.03.002. Epub 2018 Mar 5.
Mammalian cytochromes P450 are an important class of enzymes involved in the biotransformation of many endo- and exogenous compounds. Cytochrome P450 isoforms are attached to the membrane of the endoplasmic reticulum or mitochondria, and their catalytic domains move along the membrane surface while being partially immersed in the membrane environment. Their active sites are connected to both the membrane and cytosolic environments via a complex network of access channels. Consequently, they can accept substrates from both environments. The membrane also supports the interactions of cytochromes P450 with their redox partners. In this review, we provide an overview of current knowledge of the structure, flexibility, and interactions with substrates and redox partners of cytochrome P450 on membranes, amalgamating information derived from both experiments and simulations.
哺乳动物细胞色素 P450 是一类重要的酶，参与许多内源性和外源性化合物的生物转化。细胞色素 P450 同工酶附着在内质网或线粒体的膜上，其催化结构域沿着膜表面移动，同时部分浸入膜环境中。它们的活性部位通过一个复杂的接入通道网络连接到膜和胞质环境。因此，它们可以接受来自两个环境的底物。膜还支持细胞色素 P450 与其氧化还原伴侣的相互作用。在这篇综述中，我们提供了对细胞色素 P450 在膜上的结构、灵活性及其与底物和氧化还原伴侣相互作用的最新知识概述，综合了实验和模拟得出的信息。
