The Structural Environment Around the Heme-Binding Site in Cyclooxygenase and Its Implication

Abstract

Cyclooxygenases (COX-1 and COX-2) have a cyclooxygenase activity involved in prostaglandin G2 (PGG2) formation and an associated peroxidase (POX) activity for the reduction of PGG2 to PGH2, which are functionally interdependent. Peroxide-mediated oxidation of the heme group at the POX active site forming an oxyferryl heme radical cation (known as Compund I) initiates the whole catalytic cycle. The heme in COX proteins is ferriprotoporphyrin IX, much of which is lost upon isolation, but can be replaced to convert apo- to holo-enzyme.