Bovine factor IX (Christmas factor) is a coagulation protein present in plasma in a precursor or inactive form. It is a glycoprotein (M, = 55,000) composed of a single polypeptide chain. Factor IX in the presence of calcium ions is converted to factor IX, by factor XI, (activated plasma thromboplastin antecedent) or a protease present in Russell’s viper venom. The activation of factor IX by the protease from Russell’s viper venom is due to the cleavage of a single internal Arg-Val peptide bond in factor IX. This leads to the formation of factor IX,,, a protein with the same molecular weight as the precursor. Factor IX,, is composed of two polypeptide chains held together by a disulfide bond(s), and these two chains have an NH,-terminal sequence of Tyr-Asn-Ser-Glyand Val-Val-Gly-Gly-. The mechanism of activation of factor IX catalyzed by the protease from Russell’s viper venom differs from that catalyzed by factor XI,. The latter enzyme activates factor IX in a two-step reaction. In the first step, an internal Arg-Ala bond is cleaved, and in the second step, an Arg-Val bond is cleaved. The second cleavage leads to the liberation of an activation peptide from the NH,-terminal portion of the heavy chain to produce factor IX,. The critical step in the activation of factor IX by both pathways is the cleavage of the same Arg-Val peptide bond and the formation of a new NH,-terminal sequence of Val-Val-Gly-Glyin the heavy chain of the enzyme which contains the active site serine residue. Factor I&w has approximately 50% of the specific activity of factor IX, in a coagulant or esterase assay, and both enzymes are inhibited by antithrombin III. A number of other purified plasma proteases were also examined for their ability to activate factor IX. Factor &,, (activated Stuart factor) catalyzed a slow but definite activation of factor IX, while the activation of factor IX by bovine kallikrein, thrombin, or factor XII, (activated Hageman factor) was negligible.
Activation of bovine factor IX (Christmas factor) by factor XIa (activated plasma thromboplastin antecedent) and a protease from Russell's viper venom.
P. Lindquist,K. Fujikawa,E. Davie
Published 1978 in Journal of Biological Chemistry
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- Publication year
1978
- Venue
Journal of Biological Chemistry
- Publication date
1978-03-25
- Fields of study
Biology, Medicine, Chemistry
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Semantic Scholar, PubMed
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