Structural Biology of Recombinant Bovine Pancreatic Phospholipase A2 and its Inhibitor Complexes

K.      Sekar

doi:10.2174/156802607780487632

Abstract

The enzyme phospholipase A2 catalyzes the cleavage of the sn-2 acyl ester bond of phospholipids, leading to the production of free fatty acids and lysophospholipids, which leads to many inflammatory disorders. In view of its pharmaceutical interest, three phospholipase A2 + inhibitor (namely, (i) L-1-O-octyl-2-heptylphosphonyl-sn-glycero-3- phosphoethanolamine, Transition State Analogue, (ii) 1-Hexadecyl-3-(trifluoroethyl)-sn-glycero-2-phosphomethanol, MJ33 and (iii) p-methoxybenzoic acid, anisic acid) complex structures have already been solved and analysed, using the data obtained from X-ray diffraction. These structures provide insight on the mode of binding of the inhibitor molecules at the active site of phospholipase A2. The knowledge of the active site geometry in these inhibitor bound structures, yield valuable information in the design of more useful therapeutic agents. This report reviews only the inhibitor bound recombinant bovine pancreatic phospholipase A2 structures solved using X-ray crystallography.

Keywords: X-ray crystallography, phospholipase A2, extra cellular, drug/inhibitor molecules, surface loop, inflammation and rheumatoid arthritis

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