Characterization of the structure and function of three phospholipases A 2 from the venom of Agkistrodon halys pallas

Abstract

Y.-C. Chen, J. M. Maraganore, I. Reardon and R. L. Heinrikson. Characterization of the structure and function of three phospholipases A 2 from the venom of Agkistrodon halys pallas. Toxicon 25, 401 – 409. 1987.—Three monomeric phospholipases A 2 with isoelectric points 4.5, 6.9 and 9.3 were purified from the venom of Agkistrodon halys pallas. The complete amino acid sequence of the acidic enzyme and partial amino acid sequences of the neutral and basic phospholipases were determined in order to relate differences in enzymatic reactivities, pharmacologic activities and cytotoxicities to aspects of structure. Studies reported here and elsewhere demonstrate that the three phospholipases A 2 exhibit pronounced differences relative to function. The acidic enzyme maintains the highest reactivity toward hydrolysis of monolayers at the air — water interface and may share a feature in common with the acidic enzyme from A. h. blomhoffii, namely the inhibition of platelet aggregation. The neutral phospholipase A 2 designated agkistrotoxin, is characterized by potent activity as a pre-synaptic neurotoxin. Agkistrotoxin is the first single polypeptide chain, neurotoxic phospholipase A 2 to be documented with a Group II disulfide pattern and, in several respects, may be considered functionally and structurally analogous to notexin from the Australian tiger snake venom. Finally, the basic enzyme exhibits the abilities to hemolyze erythrocytes and to hydrolyze phospholipids of E. coli membranes in the presence of a bactericidal-permeability-increasing protein from neutrophil sources.