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PDBsum entry 1dd0

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Oxidoreductase PDB id
1dd0
Jmol
Contents
Protein chains
552 a.a.
Ligands
NAG-NAG ×2
NAG-NAG-MAN-MAN ×2
NAG ×2
BOG ×5
PGX ×2
Waters ×767

References listed in PDB file
Key reference
Title Structural insights into the stereochemistry of the cyclooxygenase reaction.
Authors 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.
Ref. Nature, 2000, 405, 97. [DOI no: 10.1038/35011103]
PubMed id 10811226
Abstract
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.
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.
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.
The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2000, 405, 97-0) copyright 2000.
Secondary reference #1
Title Structural basis for selective inhibition of cyclooxygenase-2 by anti-Inflammatory agents.
Authors 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.
Ref. Nature, 1996, 384, 644-648.
PubMed id 8967954
Abstract
PROCHECK
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