A NOVEL TYPE OF PHOSPHOLIPASE A₂ INHIBITOR, THIELOCIN A1β, AND MECHANISM OF ACTION

Abstract

Thielocin A1β, a novel phospholipase A₂ inhibitor, was isolated from Thielavia terricola RF-143. It inhibited various phospholipase A₂s in a dose-dependent manner. Among these, group II phospholipase A₂ from rat was most sensitive to thielocin A1β (IC₅₀ = 0.0033 μM). The inhibition of phospholipase A₂ by thielocin A1β was independent of Ca²⁺ and substrate concentration. In addition, the inhibition of rat group II phospholipase A₂ was noncompetitive (Ki=0.0068 μM) and reversible. Furthermore, thielocin Al β quenched the relative fluorescent intensity of Naja naja venom phospholipase A₂ and in a dose-dependent manner; 50% quench was noted with a molar ratio of thielocin A1β/ enzyme of 2.2. These observations indicated that inhibition of phospholipase A₂ by thielocin A1β may result from direct interaction with the enzyme.