Characterization and cDNA cloning of a platelet aggregation inhibitor

Mol Cells. 2000 Aug 31;10(4):437-42.

Abstract

A novel platelet aggregation inhibitor, sal-C, was purified to homogeneity from the venom of Korean snake (Agkistrodon halys brevicaudus). Several lines of experimental evidence clearly indicated that sal-C inhibits not only the collagen-induced platelet aggregation, but also the aggregation mediated by the cell surface glycoprotein IIb-IIIa (GP IIb-IIIa). We have isolated the cDNA encoding sal-C from the cDNA library of the snake venom gland and analyzed its complete nucleotide sequence. Sal-C is a single-chain polypeptide composed of 212 amino acids including 24 cysteines. The deduced polypeptide sequence of sal-C demonstrated considerable homology to previously described protein species of the collagen-induced platelet aggregation inhibitor family. Sal-C does not have the Arg-Gly-Asp (RGD) motif, but contains the Ser-Glu-Cys-Asp sequence. Interestingly, sal-C was found to inhibit GP IIb-IIIa binding to immobilized fibrinogen which is antagonized by the typical RGD motif of disintegrins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agkistrodon / genetics*
  • Agkistrodon / metabolism*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cloning, Molecular
  • Crotalid Venoms / enzymology*
  • Crotalid Venoms / genetics
  • DNA, Complementary
  • Humans
  • Metalloendopeptidases / genetics*
  • Metalloendopeptidases / isolation & purification
  • Metalloendopeptidases / pharmacology*
  • Molecular Sequence Data
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / isolation & purification
  • Platelet Aggregation Inhibitors / pharmacology*
  • Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors
  • Sequence Analysis, DNA
  • Sequence Homology
  • Viper Venoms*

Substances

  • Crotalid Venoms
  • DNA, Complementary
  • Platelet Aggregation Inhibitors
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Viper Venoms
  • Metalloendopeptidases
  • sal-C protein, Agkistrodon halys brevicaudus