FIGURE 4.

Crystal structure of naproxen bound to mCOX-2. A, difference electron density map (F_O − F_C) contoured at 3.5σ of the COX-2 active site prior to the addition of naproxen to the model or modification of side chain positions in the binding pocket. This and other molecular graphics images were composed with PyMOL (Delano Scientific). B, stereoview of the crystal structure of naproxen (blue carbon atoms) bound at the COX-2 active site reveals that it forms extensive van der Waals contacts within the binding pocket and hydrogen-bonds, similar to flurbiprofen, to the side chains of Tyr³⁵⁵ and Arg¹²⁰. The inhibitor does not enter the side pocket into which the phenyl sulfonamide or phenyl sulfone moieties of diaryl heterocyclic compounds protrude.