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Detection of vitamin K-dependent proteins in venoms with a monoclonal antibody specific for gamma-carboxyglutamic acid.

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Author

  • Mark A. Brown
  • B Hambe
  • B Furie
  • B C Furie
  • Johan Stenflo
  • Leisa Stenberg

Summary, in English

gamma-Carboxyglutamic acid (Gla) is an unusual amino acid that is synthesized post-translationally from glutamate in a vitamin K-dependent reaction. The dicarboxylic side chain of Gla chelates Ca(2+), a property important for the biological activity of vitamin K-dependent proteins. To date, Gla-containing polypeptides have been identified in venom from two groups of organisms: elapid snakes, and snails of the genus Conus. In certain elapid snakes, a gamma-carboxylated coagulation factor Xa-like protein is a component of the venom whereas cone snails utilize Gla in a range of peptide neurotoxins. Using a monoclonal antibody that specifically recognizes Gla residues, venom samples from various organisms were screened by western blotting and immunofluorescence assays. Amino acid analyses were also performed on most samples. A survey of 21 snake species from 12 genera detected gamma-carboxylated polypeptides only in venom of snakes from the elapid subfamily Acanthophiinae. Gla-containing polypeptides were also observed in cone snail venom but not in venom or toxic salivary secretions from several other organisms. The Gla-specific antibody used here provides a simple immunochemical means to detect gamma-carboxylated polypeptides in venom and may allow new species to be identified that utilize Gla in the biosynthesis of toxic polypeptides.

Publishing year

2002

Language

English

Pages

447-453

Publication/Series

Toxicon

Volume

40

Issue

4

Document type

Journal article

Publisher

Elsevier

Topic

  • Medicinal Chemistry

Keywords

  • Biological Assay : methods
  • Anura
  • Antibodies Monoclonal : diagnostic use
  • Blood Proteins : metabolism
  • Elapid Venoms : chemistry
  • Blotting Western
  • Factor Xa : analysis : metabolism
  • Fluorescent Antibody Technique
  • Mollusk Venoms : chemistry
  • Peptides : analysis : chemistry
  • Salivary Glands : chemistry
  • Support Non-U.S. Gov't
  • Snakes
  • Snails
  • Vitamin K : pharmacology
  • Animal
  • Amphibian Venoms : chemistry
  • 1-Carboxyglutamic Acid : analysis : immunology : pharmacology

Status

Published

Research group

  • Clinical Chemistry, Malmö

ISBN/ISSN/Other

  • ISSN: 0041-0101