Vignais P V
DRDC/BBSI (UMR 5092), CEA-Grenoble, France.
Cell Mol Life Sci. 2002 Sep;59(9):1428-59. doi: 10.1007/s00018-002-8520-9.
Flavocytochrome b558 is the catalytic core of the respiratory-burst oxidase, an enzyme complex that catalyzes the NADPH-dependent reduction of O2 into the superoxide anion O2 in phagocytic cells. Flavocytochrome b558 is anchored in the plasma membrane. It is a heterodimer that consists of a large glycoprotein gp91phox (phox forphagocyte oxidase) (beta subunit) and a small protein p22phox (alpha subunit). The other components of the respiratory-burst oxidase are water-soluble proteins of cytosolic origin, namely p67phox, p47phox, p40phox and Rac. Upon cell stimulation, they assemble with the membrane-bound flavocytochrome b558 which becomes activated and generates O2-. A defect in any of the genes encoding gp91phox, p22phox, p67phox or p47phox results in chronic granulomatous disease, a genetic disorder characterized by severe and recurrent infections, illustrating the role of O2- and the derived metabolites H2O2 and HOCl in host defense against invading microorganisms. The electron carriers, FAD and hemes b, and the binding site for NADPH are confined to the gp91phox subunit of flavocytochrome b558. The p22phox subunit serves as a docking site for the cytoso lic phox proteins. This review provides an overview of current knowledge on the structural organization of the O2(-)-generating flavocytochrome b558, its kinetics, its mechanism of activation and the regulation of its biosynthesis. Homologues of gp91phox, called Nox and Duox, are present in a large variety of non-phagocytic cells. They exhibit modest O2(-)-generating oxidase activity, and some act as proton channels. Their role in various aspects of signal transduction is currently under investigation and is briefly discussed.
黄素细胞色素b558是呼吸爆发氧化酶的催化核心，该酶复合物催化吞噬细胞中依赖烟酰胺腺嘌呤二核苷酸磷酸（NADPH）将氧气还原为超氧阴离子O₂⁻。黄素细胞色素b558锚定在质膜中。它是一种异源二聚体，由一个大的糖蛋白gp91phox（吞噬细胞氧化酶的phox）（β亚基）和一个小蛋白p22phox（α亚基）组成。呼吸爆发氧化酶的其他成分是胞质来源的水溶性蛋白，即p67phox、p47phox、p40phox和Rac。细胞受到刺激后，它们与膜结合的黄素细胞色素b558组装在一起，后者被激活并产生O₂⁻。编码gp91phox、p22phox、p67phox或p47phox的任何一个基因发生缺陷都会导致慢性肉芽肿病，这是一种以严重反复感染为特征的遗传性疾病，说明了O₂⁻以及衍生代谢产物过氧化氢（H₂O₂）和次氯酸（HOCl）在宿主抵御入侵微生物中的作用。电子载体黄素腺嘌呤二核苷酸（FAD）和血红素b以及NADPH的结合位点局限于黄素细胞色素b558的gp91phox亚基。p22phox亚基作为胞质phox蛋白的对接位点。本综述概述了目前关于产生O₂⁻的黄素细胞色素b558的结构组织、其动力学、激活机制及其生物合成调控的知识。gp91phox的同源物，称为Nox和Duox，存在于多种非吞噬细胞中。它们表现出适度的产生O₂⁻的氧化酶活性，有些还充当质子通道。它们在信号转导各个方面的作用目前正在研究中，并在此进行简要讨论。
