NCF4: Proteins and Enzymes

The NADPH oxidase generates superoxide in phagocytic cells. It is important for immunity and its deficiency leads to chronic granulomatous disease (CGD) (1). p40-phox is a newly isolated cytosolic component of the nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase that copurifies with p67-phox. Preliminary evidence indicates that it is a component of the cytosolic complex (2). Maximal activation of NADPH oxidase requires formation of a complex between the p40-phox and p67-phox subunits via association of their PB1 domains. The crystal structure of the p40-phox/p67phox PB1 heterodimer reveals that both domains have a beta grasp topology and that they bind in a front-to-back arrangement through conserved electrostatic interactions between an acidic OPCA motif on p40-phox and basic residues in p67-phox (3).