Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents

The structures of unliganded murine cyclooxygenase-1 and -2 (COX-1 and COX-2) and those of complexes with flurbiprofen, indomethacin and SC-558, a selective COX-2 inhibitor, were studied using crystallography and molecular replacement methods. The results indicated that the overall structures of COX-1 and COX-2 are highly conserved although COX-2 was shown to have a much larger non-steroidal anti-inflammatory drug binding site due to the substitution of a valine for isoleucine in the active site. It was also evident that the time-dependent cyclooxygenase inhibition may proceed via more than one mechanism.