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PDBsum entry 1b8q
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Oxidoreductase
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PDB id
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1b8q
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Contents |
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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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Solution structure of the extended neuronal nitric oxide synthase pdz domain complexed with an associated peptide.
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Authors
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H.Tochio,
Q.Zhang,
P.Mandal,
M.Li,
M.Zhang.
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Ref.
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Nat Struct Biol, 1999,
6,
417-421.
[DOI no: ]
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PubMed id
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Abstract
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The PDZ domain of neuronal nitric oxide synthase (nNOS) functions as a scaffold
for organizing the signal transduction complex of the enzyme. The NMR structure
of a complex composed of the nNOS PDZ domain and an associated peptide suggests
that a two-stranded beta-sheet C-terminal to the canonical PDZ domain may
mediate its interaction with the PDZ domains of postsynaptic density-95 and
alpha-syntrophin. The structure also provides the molecular basis of recognition
of Asp-X-Val-COOH peptides by the nNOS PDZ domain. The role of the C-terminal
extension in Asp-X-Val-COOH peptide binding is investigated. Additionally, NMR
studies further show that the Asp-X-Val-COOH peptide and a C-terminal peptide
from a novel cytosolic protein named CAPON bind to the same pocket of the nNOS
PDZ domain.
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Figure 1.
Figure 1. a, Stereoview showing the best-fit superposition of
the backbone atoms (N, C  ,
and C') of the final 15 structures of the nNOS PDZ−MelR
peptide complex. The structures are superimposed against the
average structure using the residues 14−98. The MelR peptide
(VVKVDSV) is shown in pink. The  -strands
in the C-terminal extension are in orange, and the rest of the
extension is in cyan. b, Superposition of the 15 NMR structures
using the 'I
and 'II
showing the defined structure of the C-terminal extension of the
nNOS PDZ domain. c, Ribbon diagram of the nNOS PDZ−MelR
peptide complex. The secondary structural elements of the
canonical nNOS PDZ domain are labeled following the scheme of
the crystal structure of the PSD-95 PDZ domain^7. The MelR
peptide is shown in pink, and the C-terminal extension is in
yellow. The two C-terminal strands are named 'I
and 'II,
respectively.
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Figure 4.
Figure 4. Model for nNOS signal transduction complex
organization by PDZ domains. The NMDA receptors are clustered
by multiple PDZ domain containing PSD-95. The multimeric PSD-95
further couples nNOS to the NMDA receptors, allowing direct
activation of nNOS by influxes of Ca^2+. The PDZ domain of nNOS
can further recruit its binding protein such as CAPON by binding
to its C-terminal tail. The PTB domain of CAPON may bind to as
yet unknown NPXpY motif containing proteins in the signaling
pathway.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(1999,
6,
417-421)
copyright 1999.
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