Subunit structure and inhibition specificity of α-type phospholipase A2 inhibitor from Protobothrops flavoviridis

The alpha-type phospholipase A(2) inhibitor (PLI alpha) in the plasma of the Habu snake, Protobothrop flavoviridis, was shown to be a trimer of two homologous subunits, PLI alpha-A and PLI alpha-B, each of which contains one C-type lectin-like domain (CTLD). Since one molecule of trimeric PLIa binds stoichiometrically to one molecule of P. flavoviridis acidic phospholipase A(2) (PLA(2)) the trimeric structure is critical for its inhibitory activity. Hydrophobic chromatography separated the purified P. flavoviridis PLIa into four different trimeric subspecies, A(3)-PLI alpha, A(2)B-PLI alpha, AB(2)-PLI alpha, and B-3-PLI alpha, with different combinations of the two subunits. The trimeric PLIa could be reconstituted from the purified subunits, and the four different trimeric subspecies were formed through random association of the two subunits. The inhibitory activity of the PLI alpha-A homotrimer (A3-PLIa) was more specific than that of the PLI alpha-B homotrimer (B-3-PLI alpha). This difference in inhibitory properties between the two homotrimers was probably caused by the amino acid differences at residues 10-37. (c) 2007 Elsevier Ltd. All rights reserved.