|1diy, resolution 3.00Å ()|
|Ligands:||, , , , , ,|
|Related:||1cvu, 1ddx, 1prh, 1pth, 1pge|
CRYSTAL STRUCTURE OF ARACHIDONIC ACID BOUND IN THE CYCLOOXYGENASE ACTIVE SITE OF PGHS-1
Prostaglandin H synthase-1 and -2 (PGHS-1 and -2) catalyze the committed step in prostaglandin synthesis and are targets for nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin. We have determined the structure of PGHS-1 at 3 angstrom resolution with arachidonic acid (AA) bound in a chemically productive conformation. The fatty acid adopts an extended L-shaped conformation that positions the 13proS hydrogen of AA for abstraction by tyrosine-385, the likely radical donor. A space also exists for oxygen addition on the antarafacial surface of the carbon in the 11-position (C-11). While this conformation allows endoperoxide formation between C-11 and C-9, it also implies that a subsequent conformational rearrangement must occur to allow formation of the C-8/C-12 bond and to position C-15 for attack by a second molecule of oxygen.
The productive conformation of arachidonic acid bound to prostaglandin synthase., Malkowski MG, Ginell SL, Smith WL, Garavito RM, Science. 2000 Sep 15;289(5486):1933-7. PMID:10988074
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
- Malkowski MG, Ginell SL, Smith WL, Garavito RM. The productive conformation of arachidonic acid bound to prostaglandin synthase. Science. 2000 Sep 15;289(5486):1933-7. PMID:10988074