THE ROLE OF ENZYMATIC-ACTIVITY IN INHIBITION OF THE EXTRINSIC TENASE COMPLEX BY PHOSPHOLIPASE A(2) ISOENZYMES FROM NAJA-NIGRICOLLIS VENOM

Three phospholipase A(2) isoenzymes from Naja nigricollis venom inhibi t the extrinsic tenase complex. We examined the role of their enzymati c activity in this inhibition by studying the effects of native and Hi s-modified enzymes. Only CM-IV of the His-modified, catalytically inac tive proteins showed significant inhibition of the activity of the com plex. This indicates that strongly anticoagulant CM-IV inhibits the co mplex by both enzymatic and nonenzymatic mechanisms, whereas the weakl y anticoagulant isoenzymes, CM-I and CM-II, inhibit primarily by catal ytic degradation of phospholipids. This indicates a functional differe nce in the mode of inhibition between strongly and weakly anticoagulan t phospholipase A(2) enzymes.