Oxicams bind in a novel mode to the cyclooxygenase active site via a two-water-mediated h-bonding network

Abstract

Background: The oxicams are anti-inflammatory drugs targeting the cyclooxygenase enzymes. Results: Crystal complexes of mCOX-2 isoxicam, mCOX-2 meloxicam, and oCOX-1 meloxicam are solved. Conclusion: Oxicams bind to the cyclooxygenase active sites in a novel mode. Significance: The first structural description of cyclooxygenase-oxicam complexes reveal a new binding pocket of inhibitors to cyclooxygenases. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.