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首页> 外文期刊>Journal of Inorganic Biochemistry: An Interdisciplinary Journal >CYP2J2 epoxygenase membrane anchor plays an important role in facilitating electron transfer from CPR
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CYP2J2 epoxygenase membrane anchor plays an important role in facilitating electron transfer from CPR

机译:CYP2J2环氧合酶膜锚在促进CPR电子转移中起重要作用

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CYP2J2 epoxygenase is a membrane-bound cytochrome P450 primarily expressed in the heart and plays a significant role in cardiovascular diseases. The interactions of CYP2J2 with its redox partner, cytochrome P450 reductase (CPR), and with its substrates are quite complex and can have a significant effect on the kinetics of substrate metabolism. Here we show that the N-terminus of CYP2J2 plays an important role in the formation of CYP-CPR complex for subsequent electron transfer. We demonstrate that when CYP2J2-CPR are pre-incubated before the onset of reduction, the kinetics of reduction is triphasic and is of a similar order of magnitude to previously reported rates in other cytochrome P450 systems. However, when CYP2J2 and CPR form a complex during the time course of the experiment the kinetics of the fastest phase for N-terminus containing full-length CYP2J2 is 200 times faster than the kinetics of reduction of N-terminally truncated CYP2J2. Hence, we show that the N-terminus of CYP2J2 is very important to form a productive CYP-CPR complex to facilitate electron transfer. (C) 2014 Elsevier Inc. All rights reserved.
机译:CYP2J2环氧合酶是一种膜结合的细胞色素P450,主要在心脏中表达,在心血管疾病中起重要作用。 CYP2J2与它的氧化还原伙伴,细胞色素P450还原酶(CPR)及其底物之间的相互作用非常复杂,可能对底物代谢动力学产生重大影响。在这里,我们显示CYP2J2的N端在CYP-CPR复合物的形成中为后续电子转移起重要作用。我们证明当CYP2J2-CPR在还原反应发生之前进行预孵育时,还原反应动力学是三次的,并且与先前在其他细胞色素P450系统中报道的速率相似。但是,当CYP2J2和CPR在实验过程中形成复合物时,含全长CYP2J2的N末端最快相的动力学比N末端截短的CYP2J2还原的动力学快200倍。因此,我们表明CYP2J2的N端对于形成高效的CYP-CPR复合物以促进电子转移非常重要。 (C)2014 Elsevier Inc.保留所有权利。

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