The mechanism of activation of NADPH oxidase in the cell-free system: the activation process is primarily catalytic and not through the formation of a stoichiometric complex.
It is commonly assumed that activation of the superoxide-generating NADPH oxidase requires the formation of a stable complex between flavocytochrome b-245 (the gp91phox/p22phox heterodimer) and the cytosolic cofactors p47phox, p67phox and Rac2. This association is thought to convert flavocytochrome b-245, which contains the NADPH-binding site, flavin and haem centres, from an inactive into an active state. Here we provide evidence that, in the cell-free system, this activation process does not necessarily require the formation of a stable stoichiometric complex between the phox proteins. To explain this data we propose the hypothesis that p67phox (and possibly Rac2), are capable of activating flavocytochrome b-245 in a catalytic fashion, where a single molecule of p67phox (or Rac2) is capable of activating multiple flavocytochrome b-245 molecules.
Cross
A R
AR
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA. scross@scripps.edu
Erickson
R W
RW
Curnutte
J T
JT
D000818:Animals; D001665:Binding Sites; D002474:Cell-Free System; D004789:Enzyme Activation; D006801:Humans; D009249:NADP / Q000378:metabolism*; D019255:NADPH Oxidases / Q000737:chemistry / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding
D010750:Phosphoproteins; C079789:neutrophil cytosol factor 67K; D009249:NADP; D019255:NADPH Oxidases