Crystal structure of phospholipase A2 in complex with 1‐naphthaleneacetic acid

Phospholipase A2 (PLA2) is one of the rate limiting enzymes involved in the production of arachidonic acid, a potent inflammatory mediator. PLA2 is widely distributed all over the animal kingdom. It is also seen in inflammatory exudation and venoms of different organisms. The studies demonstrated that PLA2 inhibitors have broad spectrum activities that they can either be used against inflammation or envenomation. In this study, the inhibitory activity of 1‐napthaleneacetic acid (NAA) against porcine pancreatic PLA2 has been explained through isothermal titration calorimetry and enzyme kinetics studies. The atomic level of interactions of NAA with PLA2 was also studied using X‐ray crystallography. Apart from these findings, the theoretical binding affinities and mode of interactions of two naphthalene‐based NSAIDs such as naproxen (NAP) and nabumetone (NAB) were studied through molecular modeling. The studies proved that the selected ligands are binding at the doorway of the active site cleft and hindering the substrate entry to the active site. The study brings out a potential scaffold for the designing of broad spectrum PLA2 inhibitors which can be used for inflammation or envenomation. © 2018 IUBMB Life, 70(10):995–1001, 2018