The first phospholipase inhibitor from the serum of Vipera ammodytes ammodytes.
Ammodytoxins are neurotoxic secretory phospholipase A(2) molecules, some of the most toxic components of the long-nosed viper (Vipera ammodytes ammodytes) venom. Envenomation by this and by closely related vipers is quite frequent in southern parts of Europe and serotherapy is used in the most severe cases. Because of occasional complications, alternative medical treatment of envenomation is needed. In the present study, ammodytoxin inhibitor was purified from the serum of V. a. ammodytes using two affinity procedures and a gel exclusion chromatography step. The ammodytoxin inhibitor from V. a. ammodytes serum consists of 23- and 25-kDa glycoproteins that form an oligomer, probably a tetramer, of about 100 kDa. N-terminal sequencing and immunological analysis revealed that both types of subunit are very similar to gamma-type secretory phospholipase A(2) inhibitors. The ammodytoxin inhibitor from V. a. ammodytes serum is a potent inhibitor of phospholipase activity and hence probably also the neurotoxicity of ammodytoxins. Discovery of the novel natural inhibitor of these potent secretory phospholipase A(2) toxins opens up prospects for the development of new types of small peptide inhibitors for use in regulating the physiological and pathological activities of secretory phospholipases A(2).
Sribar
Jernej
J
Department of Molecular and Biomedical Sciences, Jozef Stefan Institute, Ljubljana, Slovenia.
Kovacic
Lidija
L
Draskovic
Petra
P
Faure
Grazyna
G
Krizaj
Igor
I
D000345:Affinity Labels / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002846:Chromatography, Affinity; D002850:Chromatography, Gel; D004795:Enzyme Stability; D006023:Glycoproteins / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007457:Iodine Radioisotopes / Q000378:metabolism; D008969:Molecular Sequence Data; D008970:Molecular Weight; D064801:Phospholipase A2 Inhibitors; D054467:Phospholipases A2 / Q000737:chemistry* / Q000145:classification / Q000302:isolation & purification*; D011485:Protein Binding; D020539:Sequence Analysis, Protein; D020349:Surface Plasmon Resonance; D013696:Temperature; D013997:Time Factors; D014757:Viper Venoms / Q000097:blood* / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism
D000345:Affinity Labels; D006023:Glycoproteins; D007457:Iodine Radioisotopes; D064801:Phospholipase A2 Inhibitors; D014757:Viper Venoms; D054467:Phospholipases A2