Skip to main content
Skip to main content
Proc Natl Acad Sci U S A. 1974 Jul; 71(7): 2730–2733.
doi: 10.1073/pnas.71.7.2730
PMCID: PMC388542
PMID: 4528109

Vitamin K Dependent Modifications of Glutamic Acid Residues in Prothrombin

Johan Stenflo,* Per Fernlund,* William Egan,† and Peter Roepstorff‡
Author information Copyright and License information PMC Disclaimer

Abstract

A tetrapeptide, residues 6 to 9 in normal prothrombin, was isolated from the NH2-terminal, Ca2+-binding part of normal prothrombin. The electrophoretic mobility of the peptide was too high to be explained entirely by its amino-acid composition. According to 1H nuclear magnetic resonance spectroscopy and mass spectrometry, the peptide contained two residues of modified glutamic acid, γ-carboxyglutamic acid (3-amino-1,1,3-propanetricarboxylic acid), a hitherto unidentified amino acid. This amino acid gives normal prothrombin the Ca2+-binding ability that is necessary for its activation. Observations indicate that abnormal prothrombin, induced by the vitamin K antagonist, dicoumarol, lacks these modified glutamic acid residues and that this is the reason why abnormal prothrombin does not bind Ca2+ and is nonfunctioning in blood coagulation.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (788K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

 
icon of scanned page 2730
2730
icon of scanned page 2731
2731
icon of scanned page 2732
2732
icon of scanned page 2733
2733
 

Images in this article

Image

Image
on p.2731

Image

Image
on p.2732

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  • Niléhn JE, Ganrot PO. Plasma prothrombin during treatment with Dicumarol. I. Immunochemical determination of its concentration in plasma. Scand J Clin Lab Invest. 1968;22(1):17–22. [PubMed] [Google Scholar]
  • Ganrot PO, Niléhn JE. Plasma prothrombin during treatment with Dicumarol. II. Demonstration of an abnormal prothrombin fraction. Scand J Clin Lab Invest. 1968;22(1):23–28. [PubMed] [Google Scholar]
  • Josso F, Lavergne JM, Gouault M, Prou-Wartelle O, Soulier JP. Différents états moléculaires du facter II (prothrombine). Leur étude à l'aide de la staphylocoagulase et d'anticorps anti-facteur II. I. Le facteur II chez les sujets traités par les antagonistes de la vitamine K. Thromb Diath Haemorrh. 1968 Nov 15;20(1):88–98. [PubMed] [Google Scholar]
  • Stenflo J. Dicumarol-induced prothrombin in bovine plasma. Acta Chem Scand. 1970;24(10):3762–3763. [PubMed] [Google Scholar]
  • Stenflo J, Ganrot PO. Vitamin K and the biosynthesis of prothrombin. I. Identification and purification of a dicoumarol-induced abnormal prothrombin from bovine plasma. J Biol Chem. 1972 Dec 25;247(24):8160–8166. [PubMed] [Google Scholar]
  • Nelsestuen GL, Suttie JW. The purification and properties of an abnormal prothrombin protein produced by dicumarol-treated cows. A comparison to normal prothrombin. J Biol Chem. 1972 Dec 25;247(24):8176–8182. [PubMed] [Google Scholar]
  • Nelsestuen GL, Suttie JW. Mode of action of vitamin K. Calcium binding properties of bovine prothrombin. Biochemistry. 1972 Dec 19;11(26):4961–4964. [PubMed] [Google Scholar]
  • Stenflo J, Ganrot PO. Binding of Ca 2+ to normal and dicoumarol-induced prothrombin. Biochem Biophys Res Commun. 1973 Jan 4;50(1):98–104. [PubMed] [Google Scholar]
  • Stenflo J. Vitamin K and the biosynthesis of prothrombin. 3. Structural comparison of an NH2-terminal fragment from normal and from dicoumarol-induced bovine prothrombin. J Biol Chem. 1973 Sep 25;248(18):6325–6332. [PubMed] [Google Scholar]
  • Nelsestuen GL, Suttie JW. The mode of action of vitamin K. Isolation of a peptide containing the vitamin K-dependent portion of prothrombin. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3366–3370. [PMC free article] [PubMed] [Google Scholar]
  • Vilkas E, Lederer E. N-methylation de peptides par a methode de Hakomori. Structure du mycoside Cbl. Tetrahedron Lett. 1968 May;(26):3089–3092. [PubMed] [Google Scholar]
  • Morris HR. Studies towards the complete sequence determination of proteins by mass spectrometry; a rapid procedure for the successful permethylation of histidine containing peptides. FEBS Lett. 1972 May 15;22(3):257–260. [PubMed] [Google Scholar]
  • Gitel SN, Owen WG, Esmon CT, Jackson CM. A polypeptide region of bovine prothrombin specific for binding to phospholipids. Proc Natl Acad Sci U S A. 1973 May;70(5):1344–1348. [PMC free article] [PubMed] [Google Scholar]
  • Fujikawa K, Coan MH, Enfield DL, Titani K, Ericsson LH, Davie EW. A comparison of bovine prothrombin, factor IX (Christmas factor), and factor X (Stuart factor). Proc Natl Acad Sci U S A. 1974 Feb;71(2):427–430. [PMC free article] [PubMed] [Google Scholar]
Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences