NADPH oxidase 2 cytochrome b558 complex (p22phox–p47phox interface) (NOX2 (p22phox–p47phox))

The NADPH oxidase 2 (NOX2) cytochrome b558 complex is a multi-subunit enzyme system primarily responsible for the production of reactive oxygen species (ROS) during the respiratory burst in phagocytes (UniProt P04839). The complex consists of the membrane-bound cytochrome b558—a heterodimer of gp91phox and p22phox—and several cytosolic regulatory subunits, including p47phox, p67phox, and p40phox (UniProt P13498, P14598). A critical step in the activation of NOX2 is the translocation of p47phox to the membrane, where its tandem SH3 domains bind to the proline-rich region (PRR) of p22phox (PMID: 15689570). This protein-protein interaction (PPI) serves as a molecular switch that facilitates the assembly of the active enzyme complex. Dysregulation or overactivation of this interface is linked to oxidative stress-mediated damage in cardiovascular and neurodegenerative diseases (PMID: 29153444). Consequently, the p22phox–p47phox interface is a high-priority therapeutic target for small-molecule inhibitors, such as Phox-I, designed to block ROS production by disrupting this specific assembly step (PMID: 25100793).

Other names

Cytochrome b558gp91phox-p22phox complexp47phox-p22phox interactionNCF1-CYBA interfaceNOX2 assembly interfacePhagocyte NADPH oxidase complex

Disruption of the protein-protein interaction between the p47phox SH3 domains and the p22phox proline-rich region, preventing the assembly and activation of the NADPH oxidase 2 complex (PMID: 25100793).