1NG2

Structure of autoinhibited p47phox

Summary for 1NG2

• Entry DOI: 10.2210/pdb1ng2/pdb
• Related: 1OV3
• Descriptor: Neutrophil cytosolic factor 1 (2 entities in total)
• Functional Keywords: p47phox, autoinhibited, sh3 domain, nadph oxidase, oxidoreductase activator
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P14598
• Total number of polymer chains: 1
• Total formula weight: 22062.74

Authors

Groemping, Y.,Lapouge, K.,Smerdon, S.J.,Rittinger, K. (deposition date: 2002-12-16, release date: 2003-05-20, Last modification date: 2024-05-22)

Primary citation

Groemping, Y.,Lapouge, K.,Smerdon, S.J.,Rittinger, K.
Molecular basis of phosphorylation-induced activation of the NADPH oxidase
Cell(Cambridge,Mass.), 113:343-355, 2003

PubMed Abstract: The multi-subunit NADPH oxidase complex plays a crucial role in host defense against microbial infection through the production of reactive oxygen species. Activation of the NADPH oxidase requires the targeting of a cytoplasmic p40-p47-p67(phox) complex to the membrane bound heterodimeric p22-gp91(phox) flavocytochrome. This interaction is prevented in the resting state due to an auto-inhibited conformation of p47(phox). The X-ray structure of the auto-inhibited form of p47(phox) reveals that tandem SH3 domains function together to maintain the cytoplasmic complex in an inactive form. Further structural and biochemical data show that phosphorylation of p47(phox) activates a molecular switch that relieves the inhibitory intramolecular interaction. This permits p47(phox) to interact with the cytoplasmic tail of p22(phox) and initiate formation of the active, membrane bound enzyme complex.

PubMed: 12732142
DOI: 10.1016/S0092-8674(03)00314-3

Experimental method

X-RAY DIFFRACTION (1.7 Å)