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PDBsum entry 1dm7
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Oxidoreductase
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PDB id
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1dm7
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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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Crystal structures of bovine endothelial nitric oxide synthase heme domain complexed with various inhibitors
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Authors
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C.S.Raman,
H.Li,
P.Martasek,
G.J.Southan,
B.S.S.Masters,
T.L.Poulos.
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Ref.
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To be Published ...
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Secondary reference #1
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Title
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Crystal structure of constitutive endothelial nitric oxide synthase: a paradigm for pterin function involving a novel metal center.
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Authors
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C.S.Raman,
H.Li,
P.Martásek,
V.Král,
B.S.Masters,
T.L.Poulos.
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Ref.
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Cell, 1998,
95,
939-950.
[DOI no: ]
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PubMed id
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Figure 5.
Figure 5. Cooperativity and Molecular Mimicry in eNOS(A)
Cross talk between H[4]B and L-Arg mediated by the heme
propionate (Se-edge data). The guanidinium and amino groups of
L-Arg are held in place by H-bonding with the conserved Glu-363.
The amino group also H-bonds with a heme propionate. H[4]B
H-bonds directly with the heme propionate, while the pteridine
ring is sandwiched between Phe-462 in one monomer and Trp-449 in
another, respectively.(B) L-Arg is a structural mimic of H[4]B
at the pterin-binding site when SEITU is bound at the active
site (-H[4]B, +SEITU data). L-Arg binds to the pterin site and
exquisitely mimics the H[4]B interaction with eNOS ([A] and
Figure 4). The specific interaction of the potent inhibitor,
SEITU, at the active site is mediated by a pair of bifurcated
H-bonds to Glu-363. Two water molecules bridge between the
inhibitor and heme propionate. The ethyl group of the inhibitor
forms nonbonded contacts with Val-338 and Phe-355. The ureido
sulfur is positioned 3.5 Å and 4.0 Å above heme
pyrrole B-ring nitrogen and the heme iron, respectively.
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Figure 7.
Figure 7. Proposed Mechanism for Pterin in NO
BiosynthesisThe uniqueness of the H[4]B–eNOS interaction
(Figure 4) and the ability to bind L-Arg at the pterin site
present a strong case for the involvement of a pterin radical in
NOS catalysis and rule out the possibility of H[4]B ↔ qH[2]B
cycling during NO biosynthesis. R represents the dihydroxypropyl
side chain at the C6 position on the pterin ring.
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The above figures are
reproduced from the cited reference
with permission from Cell Press
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Secondary reference #2
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Title
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Structure of nitric oxide synthase oxygenase dimer with pterin and substrate.
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Authors
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B.R.Crane,
A.S.Arvai,
D.K.Ghosh,
C.Wu,
E.D.Getzoff,
D.J.Stuehr,
J.A.Tainer.
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Ref.
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Science, 1998,
279,
2121-2126.
[DOI no: ]
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PubMed id
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Figure 1.
Fig. 1. NOS[ox]  -  fold, dimer
assembly, and likely interaction surface for NOS[red] and
caveolin. (A) The symmetric iNOS[ox] dimer viewed along the
crystallographic twofold axis, showing left (and^ right)
subunits with orange (yellow) winged sheets and
flanking blue (cyan) helices. Ball-and-stick models (white bonds
with red^ oxygen, blue nitrogen, yellow sulfur, and purple iron
atoms) highlight active-center hemes (left-most and right-most),
interchain disulfide^ bonds (center, foreground), pterin
cofactors (white, left-center and right-center), and substrate
L-Arg (green left and magenta^ right). The NH[2]-terminal ends
contribute hairpins
(center top and bottom) to the dimer interface, and the
COOH-termini (lower left and upper right) lie 85 Å apart.
Gray loops (residues 101^ to 107) are disordered. (B) iNOS[ox]
dimer shown rotated^ 90° about a horizontal axis from (A).
Each heme is cupped between the inward-facing palm (webbed sheet) and
thumb (magenta loop in front of left heme and green loop behind
right heme) of the^ "catcher's mitt" subunit fold. (C)
Solvent-accessible surface^ (29) of the iNOS[ox] dimer (one
subunit red, one subunit blue) oriented as in (B) and
color-coded by residue conservation (paler to more saturated
represents less conserved to more conserved) in NOS[ox]
sequences of known species and isozymes. The heme (white^ tubes)
is also solvent-exposed on the side (left subunit) opposite^ the
active-center channel (right subunit) and surrounded by a^
highly conserved hydrophobic surface for NOS[red] and caveolin
binding. (Stereo variations of Figs.
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Figure 5.
Fig. 5. Proposed L-Arg-assisted NOS oxygen activation. First,
substrate L-Arg (only guanidinium shown) donates a proton to
peroxo-iron, facilitating O-O bond cleavage and conversion to a
proposed oxo-iron(IV)  -cation
radical species, which then rapidly hydroxylates the^ neutral
guanidinium to NOH-L-Arg, possibly through a radical-based^
mechanism (3).
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The above figures are
reproduced from the cited reference
with permission from the AAAs
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Secondary reference #3
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Title
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Efficient formation of nitric oxide from selective oxidation of n-Aryl n'-Hydroxyguanidines by inducible nitric oxide synthase.
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Authors
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A.Renodon-Cornière,
J.L.Boucher,
S.Dijols,
D.J.Stuehr,
D.Mansuy.
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Ref.
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Biochemistry, 1999,
38,
4663-4668.
[DOI no: ]
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PubMed id
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