1DDX

CRYSTAL STRUCTURE OF A MIXTURE OF ARACHIDONIC ACID AND PROSTAGLANDIN BOUND TO THE CYCLOOXYGENASE ACTIVE SITE OF COX-2: PROSTAGLANDIN STRUCTURE

Summary for 1DDX

• Entry DOI: 10.2210/pdb1ddx/pdb
• Related: 1CQE 1CVU 1DCX 1DD0 5COX 6COX
• Descriptor: PROTEIN (PROSTAGLANDIN H2 SYNTHASE-2), 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: cox-2, cyclooxygenase, prostaglandin, arachidonate, endoperoxide, oxidoreductase
• Biological source: Mus musculus (house mouse)
• Total number of polymer chains: 4
• Total formula weight: 260100.29

Authors

Kiefer, J.R.,Pawlitz, J.L.,Moreland, K.T.,Stegeman, R.A.,Gierse, J.K.,Stevens, A.M.,Goodwin, D.C.,Rowlinson, S.W.,Marnett, L.J.,Stallings, W.C.,Kurumbail, R.G. (deposition date: 1999-11-11, release date: 2000-05-16, Last modification date: 2024-11-20)

Primary citation

Kiefer, J.R.,Pawlitz, J.L.,Moreland, K.T.,Stegeman, R.A.,Hood, W.F.,Gierse, J.K.,Stevens, A.M.,Goodwin, D.C.,Rowlinson, S.W.,Marnett, L.J.,Stallings, W.C.,Kurumbail, R.G.
Structural insights into the stereochemistry of the cyclooxygenase reaction.
Nature, 405:97-101, 2000

PubMed 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.

PubMed: 10811226
DOI: 10.1038/35011103

Experimental method

X-RAY DIFFRACTION (3 Å)