Dynamic interaction between membrane-bound full-length cytochrome P450 and cytochrome b5 observed by solid-state NMR spectroscopy.
Dynamic interaction between membrane-bound full-length cytochrome P450 and cytochrome b5 observed by solid-state NMR spectroscopy.
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DOI：
10.1038/srep02538
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发表时间：
2013
影响因子：
4.6
通讯作者：
Ramamoorthy, Ayyalusamy
中科院分区：
文献类型：
--
作者：
Yamamoto, Kazutoshi;Duerr, Ulrich H. N.;Xu, Jiadi;Im, Sang-Choul;Waskell, Lucy;Ramamoorthy, Ayyalusamy
细胞色素P450家族的微粒体单加氧酶存在于所有的生物界，在代谢和异物、毒性和70%的临床使用药物的分解中起着核心作用。全长细胞色素-b5已被证明对细胞色素-P450的催化活性很重要。尽管了解这两个膜相关蛋白之间的相互作用具有重要意义，但关于全长细胞色素-P450和细胞色素-b5-P450复合体的高分辨率结构信息有限。在这里，我们报道了一种嵌入在磁性排列的双细胞中的功能性~72 kDa细胞色素-b5-P450复合体的结构研究，而不必冷冻样品。功能性和固态核磁共振数据揭示了流体层相双层中蛋白质之间的相互作用。此外，我们的数据推断，细胞色素-b5跨膜区的骨架结构和几何形状并没有因为它与细胞色素-P450的相互作用而显著改变，而细胞色素-b5的迁移率显著降低。
Microsomal monoxygenase enzymes of the cytochrome-P450 family are found in all biological kingdoms, and play a central role in the breakdown of metabolic as well as xenobiotic, toxic and 70% of the drugs in clinical use. Full-length cytochrome-b5 has been shown to be important for the catalytic activity of cytochrome-P450. Despite the significance in understanding the interactions between these two membrane-associated proteins, only limited high-resolution structural information on the full-length cytochrome-P450 and the cytochromes-b5-P450 complex is available. Here, we report a structural study on a functional ~72-kDa cytochromes-b5-P450 complex embedded in magnetically-aligned bicelles without having to freeze the sample. Functional and solid-state NMR (Nuclear Magnetic Resonance) data reveal interactions between the proteins in fluid lamellar phase bilayers. In addition, our data infer that the backbone structure and geometry of the transmembrane domain of cytochrome-b5 is not significantly altered due to its interaction with cytochrome-P450, whereas the mobility of cytochrome-b5 is considerably reduced.
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影响因子：
2.8
作者：
Dvinskikh, SV;Yamamoto, K;Ramamoorthy, A
通讯作者：
Ramamoorthy, A
影响因子：
2.9
作者：
Sato, Takeshi;Pallavi, Payal;Smith, Steven O.
通讯作者：
Smith, Steven O.
影响因子：
2.8
作者：
Yamamoto, K;Dvinskikh, SV;Ramamoorthy, A
通讯作者：
Ramamoorthy, A
DOI：
10.1073/pnas.1834523100
发表时间：
2003-09-16
影响因子：
11.1
作者：
Luca, S;White, JF;Baldus, M
通讯作者：
Baldus, M
影响因子：
64.8
作者：
Morrison, Emma A.;DeKoster, Gregory T.;Dutta, Supratik;Vafabakhsh, Reza;Clarkson, Michael W.;Bahl, Arjun;Kern, Dorothee;Ha, Taekjip;Henzler-Wildman, Katherine A.
通讯作者：
Henzler-Wildman, Katherine A.