Crystal structure of porcine pancreatic phospholipase A2 in complex with 2-methoxycyclohexa-2-5-diene-1,4-dione

Abstract

Curcumin possess anti-inflammatory activity. In this study, the binding of curcumin with PLA2 was studied using X-ray crystallography. Since the electron density found at the active site did not match with curcumin, 2-methoxycyclohexa-2-5-diene-1,4-dione (MCW) (the photodegraded product of curcumin) was fitted in the unexplained electron density. To understand the binding mode of actual curcumin, molecular docking study was carried out. The crystallographic and docked structures were superimposed with respect to the ligand position and it was found that curcumin was binding in the hydrophobic cavity of PLA2 with a binding energy of−16.81 Kcal/mol. The binding mode was of such a nature that it prevented the entry of the substrate to the hydrophobic active site. This study indicates that curcumin can act as an inhibitor of PLA2. An animated Interactive 3D Complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:FLS:1.