Cyclooxygenase‐2 and its regulation in inflammation

Abstract

530 in COX-1 or Ser 516 in (The different numbers for similarly placed residues in the two isoforms is due to the longer N terminal sequence in COX-l; the numbering for COX-1 is thus about 14 in advance of that for COX-2.) Mutation of serine to alanine in either isoform altered neither Km nor PG production but did confer protection against the irreversi- ble inhibition caused by aspirin, since alanine cannot be acetylated. 29 However, mutation of serine to asparagine (isosteric with acetylated serine) has a strikingly differential effect; the COX-1 mutant lost cyclo-oxygenase activity whereas the COX-2 mutant retained full activity Cyclooxygenase-2 and its regulation in inflammation and an unchanged Km. Substitution with a larger not important in binding of substrate as marked amino acid, glutamine, abolished cyclo-oxygemutations at this site (Val to Lys or Glu) did not nase activity in both isoforms. 28'29 materially alter Km for AA of the COX-2 Another indication of the larger active site in protein. This compound irreversibly gested by the larger substrate binding site in inhibits the production of PGs by COX-1 or COX-2 had an unexpected outcome. It was COX-2 through the acetylation of Ser 530 or Ser argued that, as the acetylation of