A sesquiterpene furanoic acid (SFA) marine natural product isolated from soft corals of the genus Sinularia (Bowden et al., Aust J Chem 36: 371-376, 1983) was found to inactivate bee venom phospholipase A2 (bvPLA2, EC 184.108.40.206) in vitro. In this study, we characterized the kinetics of inactivation of bvPLA2 by this compound. The apparent IC50 value was 0.5 microM, and the inactivation of bvPLA2 was time dependent. The drug-enzyme binding appeared to be of a non-competitive, high-affinity nature that was irreversible by aqueous dialysis. The inactivation was prevented by the simultaneous addition of excess lysophosphatidylcholine (lysoPC) during the initial binding step, suggesting that modification of the enzyme by SFA occurs at or near the substrate binding site. Activation of bvPLA2 was observed with lysoPC addition at concentrations equimolar to bvPLA2 and higher. Saturation of activation occurred at concentrations greater than 10 microM lysoPC, and preincubation of bvPLA2 with 100 microM lysoPC did not inhibit the enzyme. Analysis of the post-incubation mixture of SFA-inhibited enzyme in the presence of lysoPC revealed the presence of unaltered enzyme exhibiting typical Michaelis-Menten kinetics. The significance of these observations is discussed in light of the recent discussion by Ortiz on the manoalide binding site on bvPLA2.