Degtyarenko K N
International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
Protein Eng. 1995 Aug;8(8):737-47. doi: 10.1093/protein/8.8.737.
All known P450-containing monooxygenase systems share common structural and functional domain architecture. Apart from P450 itself, these systems can comprise several fundamentally different protein components or domains, all of which are shared by other multicomponent/multidomain enzyme systems with various functions: FAD flavoprotein or domain, FMN domain, Fe2S2 ferredoxin, Fe3S4 ferredoxin, and cytochrome b5. Either FMN domain, ferredoxins or cytochrome b5 serve as the electron transport intermediate between the FAD domain and P450. The molecular evolution of both P450-containing systems and of each particular component does not follow phylogeny in general. Gene fusion and horizontal gene transfer events can lead to the appearance of novel redox chains in the same manner that artificial chimeric proteins can be constructed by humans. Recent studies using genetic and protein engineering techniques to investigate the separate domains and their interaction are described.
所有已知含细胞色素P450的单加氧酶系统都具有共同的结构和功能域结构。除了细胞色素P450本身外,这些系统还可包含几种根本不同的蛋白质组分或结构域,所有这些都为具有各种功能的其他多组分/多结构域酶系统所共有:黄素腺嘌呤二核苷酸(FAD)黄素蛋白或结构域、黄素单核苷酸(FMN)结构域、Fe2S2铁氧化还原蛋白、Fe3S4铁氧化还原蛋白和细胞色素b5。FMN结构域、铁氧化还原蛋白或细胞色素b5均可作为FAD结构域与细胞色素P450之间的电子传递中间体。一般来说,含细胞色素P450的系统以及每个特定组分的分子进化并不遵循系统发育。基因融合和水平基因转移事件能够导致新的氧化还原链出现,其方式与人类构建人工嵌合蛋白相同。文中描述了利用遗传和蛋白质工程技术研究各个结构域及其相互作用的最新研究情况。