(Received: July 21, 2005; Accepted for publication: October 24, 2005; Published on Web: April 5, 2006)
The phagocyte NADPH oxidase complex plays a crucial role in host defense against microbial infection through the production of reactive oxygen species. Key to the activation of NADPH oxidase is cytoplasmic subunit p47phox, which includes tandem SH3 domains and the polybasic region (Figure 1). Recently, the crystal structures of the active and inactive states of p47phox were determined, conformational change that mediates these two structures remains to be elucidated. Our simulations revealed that phosphorylations of Ser303, 304, and 328, which are important for activation of p47phox, contribute to structural changes in the region that is isolated from these serine residues. Additionally, it is concluded that the ligand exchange of p47phox in activation of NADPH oxidase is induced by interaction between the membrane subunit p22phox and N-terminal SH3 domain of p47phox that was exposed to solvent by phosphorylations.
Keywords: Molecular dynamics simulation, NADPH oxidase, SH3 domain, Phosphorylation
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