Competitive inhibition of interfacial catalysis by phospholipase A2: differential interaction of inhibitors with the vesicle interface as a controlling factor of inhibitor potency

Abstract

Phospholipid analogues containing a phosphonate in place of the ester at the sn-2 position have been previously shown to be tight-binding competitive inhibitors of secreted phospholipases A 2 . Variants of these compounds in which the structure of the phospholipid polar head group has been changed were prepared and analyzed as inhibitors of the phospholipases A 2 from the and cobra venom, porcine and bovine pancreas, and human synovial fluid. Kinetic measurements of inhibitor potencies were carried out using negatively charged substrate vesicles under conditions in which the enzyme undergoes catalysis without desorption from the vesicle (scooting mode)