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. 1974 Jul;71(7):2730–2733. doi: 10.1073/pnas.71.7.2730

Vitamin K Dependent Modifications of Glutamic Acid Residues in Prothrombin

Johan Stenflo *, Per Fernlund *, William Egan †, Peter Roepstorff ‡
PMCID: PMC388542  PMID: 4528109

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.

Keywords: proton magnetic resonance spectroscopy, mass spectrometry

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Selected References

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

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