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PDBsum entry 4nos
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Oxidoreductase
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PDB id
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4nos
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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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Structural characterization of nitric oxide synthase isoforms reveals striking active-Site conservation.
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Authors
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T.O.Fischmann,
A.Hruza,
X.D.Niu,
J.D.Fossetta,
C.A.Lunn,
E.Dolphin,
A.J.Prongay,
P.Reichert,
D.J.Lundell,
S.K.Narula,
P.C.Weber.
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Ref.
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Nat Struct Biol, 1999,
6,
233-242.
[DOI no: ]
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PubMed id
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Abstract
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Crystal structures of human endothelial nitric oxide synthase (eNOS) and human
inducible NOS (iNOS) catalytic domains were solved in complex with the arginine
substrate and an inhibitor S-ethylisothiourea (SEITU), respectively. The small
molecules bind in a narrow cleft within the larger active-site cavity containing
heme and tetrahydrobiopterin. Both are hydrogen-bonded to a conserved glutamate
(eNOS E361, iNOS E377). The active-site residues of iNOS and eNOS are nearly
identical. Nevertheless, structural comparisons provide a basis for design of
isozyme-selective inhibitors. The high-resolution, refined structures of eNOS
(2.4 A resolution) and iNOS (2.25 A resolution) reveal an unexpected structural
zinc situated at the intermolecular interface and coordinated by four cysteines,
two from each monomer.
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Figure 1.
Figure 1. Electron density maps in the immediate vicinity of the
zinc (a,b ) or BH[4] (c,d), contoured at 1.2  (green)
and 3.6 (purple).
(Left panels) Experimental electron density maps after
density modification. (Right panels) 2(F[obs] -F[calc]) electron
density maps after refinement. The final model in a
ball-and-stick representation is superposed on the maps. a,b
Electron density maps in the immediate vicinity of the zinc for
iNOS[ox] and eNOS[ox], respectively. The maps clearly define the
zinc atom and its coordination. Model colors and orientation as
in Fig. 6. c,d Electron density maps in the immediate vicinity
of BH[4], iNOS[ox] and eNOS[ox], respectively. All figures were
generated using MOLSCRIPT^40 and RASTER3D^41.
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Figure 2.
Figure 2. Structures of a, eNOS[ox] and b, iNOS[ ox] monomers
shown as ribbon diagrams, along with heme, BH[4] and either the
arginine substrate for eNOS[ox] or the inhibitor SEITU for
iNOS[ox], drawn in a ball-and-stick representation. Both
structures are in a similar orientation In this view, the heme
propionate groups are facing away from the viewer BH[4] is
located farther down the cavity and the cavity entrance is on
the opposite side of the monomer. The colors are consistent with
Fig. 3. (a) eNOS[ ox] colored according to each subdomain. (b)
iNOSox painted with the Hue Saturation Brightness color wheel
starting with magenta at the N-terminal residue to red at the
C-terminus.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(1999,
6,
233-242)
copyright 1999.
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