Prostaglandin endoperoxide H synthase, COX 2, converts arachidonic acid (AA) to prostaglandin endoperoxide H2. PGHSs are targets for NSAIDs and COX-2 specific inhibitors called coxibs. PGHS-2 is a sequence homodimer. Each monomer of the enzyme has a peroxidase and a COX active site. The COX enzymes catalyze the conversion of arachidonic acid to prostaglandins in a two steps. First, hydrogen is abstracted from carbon 13 of arachidonic acid, and then two molecules of oxygen are added by the COX-2, giving PGG2. Second, PGG2 is reduced to PGH2 in the peroxidase active site. The synthesized PGH2 is converted to prostaglandins (PGD2, PGE2, PGF2α), prostacyclin (PGI2), or thromboxane A2 by tissue-specific isomerases. Both the peroxidase and the cyclooxygenase activities are inactivated during catalysis by mechanism-based, first-order processes, which means that PGHS-2 peroxidase or cyclooxygenase activities fall to zero within 1–2 minutes, even in the presence of sufficient substrates.
enzyme binding; heme binding; heme binding; lipid binding; metal ion binding; oxidoreductase activity; oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen; peroxidase activity; peroxidase activity; peroxidase activity; prostaglandin-endoperoxide synthase activity;