On the geometry of leukocyte NADPH-oxidase, a membrane flavoenzyme: Inferences from the structure of glutathione reductase

Abstract

Using the structure of glutathione reductase as a model, we suggest the following topography for leukocyte NADPH-oxidase: The binding sites of NADPH and O 2 are separated from each other by the flavin ring and are thus exposed to opposite sides of the plasma membrane. This model supports the concept that O − 2 is formed at the membrane facing the extracellular or phagosomal space, respectively. The fate of the proton produced in the reaction NADPH + 2 O 2 → NADP + 2 O − 2 + H + is also discussed in light of our model. NAD(P)H-oxidases possessing the topography of glutathione reductase may establish transmembrane proton gradients. Consequently our model suggests that leukocyte NADPH-oxidase produces not only the O − 2 burst but also a proton burst.