Three-dimensional structure of human cyclooxygenase (hCOX)-1

The beneficial effects of Cyclooxygenases -1 and -2 (COXs) inhibitors on human health are known since many years. Nevertheless, COXs, particularly COX-1, are involved in a plethora of human diseases (i.e., cardiovascular and neurodegenerative disease, inflammatory syndrome) [1]. COXs catalyze the first step in the biosynthesis of prostaglandins (PGs), mainly key mediators of inflammatory response. Structural COX-1 characterization deals with the ovine isoenzyme [2], easier to produce in milligramquantities than human enzyme and crystallizes readily. We achieved the long-sought structure of the human cyclooxygenase-1 (hCOX-1), refined to an R/Rfree of 20.82/26.37, at 3.36 Å resolution (Figure 1) [3]. hCOX-1 3D structure provides a detailed picture of the enzyme active site and the amino acid residues crucial for inhibitor/substrate binding and catalytic activity, essential to design and develop new and highly selective COX-1 inhibitors of enhanced therapeutic index that will be the focus of the oral presentation.