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PDBsum entry 1cvu
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Oxidoreductase/peptide
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PDB id
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1cvu
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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 insights into the stereochemistry of the cyclooxygenase reaction.
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Authors
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J.R.Kiefer,
J.L.Pawlitz,
K.T.Moreland,
R.A.Stegeman,
W.F.Hood,
J.K.Gierse,
A.M.Stevens,
D.C.Goodwin,
S.W.Rowlinson,
L.J.Marnett,
W.C.Stallings,
R.G.Kurumbail.
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Ref.
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Nature, 2000,
405,
97.
[DOI no: ]
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PubMed id
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Abstract
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Cyclooxygenases are bifunctional enzymes that catalyse the first committed step
in the synthesis of prostaglandins, thromboxanes and other eicosanoids. The two
known cyclooxygenases isoforms share a high degree of amino-acid sequence
similarity, structural topology and an identical catalytic mechanism.
Cyclooxygenase enzymes catalyse two sequential reactions in spatially distinct,
but mechanistically coupled active sites. The initial cyclooxygenase reaction
converts arachidonic acid (which is achiral) to prostaglandin G2 (which has five
chiral centres). The subsequent peroxidase reaction reduces prostaglandin G2 to
prostaglandin H2. Here we report the co-crystal structures of murine
apo-cyclooxygenase-2 in complex with arachidonic acid and prostaglandin. These
structures suggest the molecular basis for the stereospecificity of
prostaglandin G2 synthesis.
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Figure 2.
Figure 2: COX-2 dimer interface solvent channel. The two
monomers (coloured green and blue) of the COX-2 dimer are shown
from the membrane face (a) or side (b). Cyclooxygenase and
peroxidase active sites are marked by AA (red) and haem
molecules (orange, superimposed onto the H207A-AA structure),
respectively. Solvent molecules are shown as yellow spheres.
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Figure 4.
Figure 4: Stereo diagram of the models of AA (a) and PGH[2] ( b)
bound at the cyclooxygenase active site. Dashed lines
indicate hydrogen bonds or ion pairs formed. The double bonds of
the AA and PGH[2] are coloured blue. Protein side chains shown
are within van der Waals contact of the ligand. The C13
pro(S)-hydrogen (purple) and pro(R)-hydrogen (gold) of AA are
shown for reference.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2000,
405,
97-0)
copyright 2000.
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Secondary reference #1
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Title
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Structural basis for selective inhibition of cyclooxygenase-2 by anti-Inflammatory agents.
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Authors
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R.G.Kurumbail,
A.M.Stevens,
J.K.Gierse,
J.J.Mcdonald,
R.A.Stegeman,
J.Y.Pak,
D.Gildehaus,
J.M.Miyashiro,
T.D.Penning,
K.Seibert,
P.C.Isakson,
W.C.Stallings.
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Ref.
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Nature, 1996,
384,
644-648.
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PubMed id
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