The N-terminus of COX-1 and its effect on cyclooxygenase-1 catalytic activity

Cyclooxygenases are encoded by COX-1 and COX-2. They share over sixty percent sequence identity in human and are similar to each other in their crystallographic structures. One major difference in the primary structure of these two isozymes is the presence of eight amino acids in the amino-terminal region of COX-1 that are not present in COX-2. The function of this amino acid sequence is unknown. In this study, a human COX-1 mutant (Delta7aa) with this sequence removed was studied in parallel with COX-1. Signal peptide cleavage, N-linked glycosylation, protein expression, distribution and dimerization were not affected by the mutation. The mutant was enzymatically active and showed the same sensitivity toward aspirin. The KM for the enzyme remained the same as COX-1. However, the V(max) of the COX-1 mutant decreased by 3.3-fold. We conclude that the COX-1 specific amino-terminal sequence has a subtle but detectable effect on COX-1 catalysis.