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...

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Bibliographic Details
Published in:Biochemical journal 1999-07, Vol.341 ( Pt 2) (2), p.251-255
Main Authors: Cross, A R, Erickson, R W, Curnutte, J T
Format: Article
Language:English
Subjects:
Animals
Binding Sites
Cell-Free System
Enzyme Activation
Humans
NADP - metabolism
NADPH Oxidases - chemistry
NADPH Oxidases - metabolism
Neutrophils - metabolism
Phosphoproteins - chemistry
Phosphoproteins - metabolism
Protein Binding
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Summary: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.
ISSN:0264-6021
1470-8728
DOI:10.1042/0264-6021:3410251