Mice − / − phox and gp91 − / − phox

The leucocyte NADPH oxidase of neutrophils is a membrane-bound enzyme that catalyses the reduction of oxygen to O(-)(2) at the expense of NADPH. The enzyme is dormant in resting neutrophils but becomes active when the cells are exposed to the appropriate stimuli. During oxidase activation, the highly basic cytosolic oxidase component p47(phox) becomes phosphorylated on several serines and migra...

The superoxide (O(·-) 2)-generating NADPH oxidase of phagocytes consists of a membrane component, cytochrome b 558 (a heterodimer of Nox2 and p22 (phox) ), and four cytosolic components, p47 (phox) , p67 (phox) , p40 (phox) , and Rac. The catalytic component, responsible for O(·-) 2 generation, is Nox2. It is activated by the interaction of the dehydrogenase region (DHR) of Nox2 with the cytoso...

The cytochrome b heavy chain (gp91-phox) is expressed exclusively in terminally differentiating myelomonocytic cells. The human gp91-phox gene spans approximately 30 kilobases, and is divided into 13 exons. A ubiquitous factor that is indistinguishable from the CCAAT-binding factor CP1 interacts in vitro with the distal gp91-phox promoter CCAAT box motif. CP1 binding is prevented, however, by a...

Maximal activation of NADPH oxidase requires formation of a complex between the p40(phox) and p67(phox) subunits via association of their PB1 domains. We have determined the crystal structure of the p40(phox)/p67(phox) PB1 heterodimer, which reveals that both domains have a beta grasp topology and that they bind in a front-to-back arrangement through conserved electrostatic interactions between...

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is an enzyme of phagocytes that produces bactericidal superoxide anion (O(2)(-)) via an electrogenic process. Proton efflux compensates for the charge movement across the cell membrane. The proton channel responsible for the H(+) efflux was thought to be contained within the gp91(phox) subunit of NADPH oxidase, but recent data do not s...

Chronic granulomatous disease (CGD) is a disorder of host defense due to genetic defects of the superoxide (O2-) generating NADPH oxidase in phagocytes. A membrane-bound cytochrome b558, a heterodimer consisting of gp91-phox and p22-phox, is a critical component of the oxidase. The X-linked form of the disease is due to defects in the gp91-phox gene. We report here biochemical and genetic analy...

Chronic granulomatous disease (CGD) is an inherited disease caused by defects in the superoxide-generating nicotinamide adenine dinucleotide phosphate (NADPH) oxidase of phagocytes. Genetic lesions in any of 4 components of this antimicrobial enzyme have been detected. Family-specific mutations are found in 3 of 4 forms of CGD due to deficiencies of the gp91-phox, p22-phox, and p67-phox genes. ...

Repressor elements in the gp91(phox) promoter are necessary to restrict tissue-specific transcription to mature phagocytes. Deletion of these elements leads to significant promoter activity in cell lines such as HEL and K562 that do not normally express gp91(phox). The -100 to +12 base pair gp91(phox) promoter region is sufficient to direct maximal de-repressed transcription in these cells. How...