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PDBsum entry 1ov3
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Oxidoreductase activator
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PDB id
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1ov3
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Contents |
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134 a.a.
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127 a.a.
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11 a.a.
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Molecular basis of phosphorylation-Induced activation of the NADPH oxidase.
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Authors
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Y.Groemping,
K.Lapouge,
S.J.Smerdon,
K.Rittinger.
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Ref.
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Cell, 2003,
113,
343-355.
[DOI no: ]
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PubMed id
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Abstract
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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.
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Figure 2.
Figure 2. Overall Structure of the Auto-Inhibitory
Conformation of p47^phox(A) Structure of the auto-inhibited
domain swapped dimer of p47^phox (156–340). The two monomers
are shown in red and green. The crystal structure of the SH3
domain of Abl (1AB0) has been overlapped onto SH3[A] and is
shown in yellow. The lower part of Figure 2A shows an expanded
view of this overlap.(B) Overall structure of the biological
monomer of auto-inhibited p47^phox. The SH3[A] and SH3[B]
domains are colored in blue and red, respectively and the
polybasic region in yellow. The secondary structural elements
are labeled according to the standard SH3 domain nomenclature.
SH3[A] and SH3[B] are related by an approximate 2-fold axis that
is perpendicular to the plane of the page.
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Figure 3.
Figure 3. P47^phox Constitutes a Novel Mode of SH3 Domain
Ligand Interactions(A) Intramolecular interactions between the
sequence R[296]GAPPRRSS[304] and the tandem SH3 domains. The
molecular surfaces of SH3[A] and SH3[B] are shown in blue-gray
and green-gray, respectively. Residues 296–303 are depicted in
stick format; Ser304 has been omitted for clarity. SH3-domain
residues involved in the intramolecular interaction are
indicated by their residue number.(B) Schematic representation
of the interactions between the RGAPPRRSS-motif and the tandem
SH3 domains. The figure was drawn with LIGPLOT (Wallace et al.,
1995). Residues of the polybasic core are shown in blue and
residues of the two SH3 domains in orange. Hydrogen bonds are
depicted as black lines with the bond distances indicated in
Å and hydrophobic interactions are shown as green
(SH3-domains) and blue (polybasic peptide) rays.
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The above figures are
reprinted
by permission from Cell Press:
Cell
(2003,
113,
343-355)
copyright 2003.
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