Reactivity of bovine blood coagulation factor IXa.beta., factor Xa.beta., and factor XIa toward fluorogenic peptides containing the activation site sequences of bovine factor IX and factor X

Biochemistry ◽  
1983 ◽  
Vol 22 (5) ◽  
pp. 1021-1029 ◽  
Author(s):  
Mario J. Castillo ◽  
Kotoku Kurachi ◽  
Norikazu Nishino ◽  
Iwao Ohkubo ◽  
James C. Powers
Keyword(s):  
Blood Coagulation ◽  
Coagulation Factor ◽  
Factor Ix ◽  
Factor X ◽  
Bovine Blood ◽  
Factor Xia ◽  
Bovine Factor ◽  
Activation Site

Prediction of the secondary structures of bovine blood coagulation factor IX, factor X, and prothrombin

1988 ◽  
Vol 7 (5) ◽  
pp. 613-632
Author(s):  
John M. Beals ◽  
Joseph Weber ◽  
Paul Derwent ◽  
Kenneth L. Grant ◽  
Francis J. Castellino
Keyword(s):  
Blood Coagulation ◽  
Coagulation Factor ◽  
Secondary Structures ◽  
Factor Ix ◽  
Factor X ◽  
Bovine Blood ◽  
Coagulation Factor Ix

scholarly journals A candidate activation pathway for coagulation factor VII

2019 ◽  
Vol 476 (19) ◽  
pp. 2909-2926
Author(s):  
Tina M. Misenheimer ◽  
Kraig T. Kumfer ◽  
Barbara E. Bates ◽  
Emily R. Nettesheim ◽  
Bradford S. Schwartz
Keyword(s):  
Tissue Factor ◽  
Blood Coagulation ◽  
Factor Viia ◽  
Coagulation Factor ◽  
Factor Ix ◽  
Factor Vii ◽  
Factor X ◽  
Contact Activation ◽  
Coagulation Factor Vii ◽  
Factor Viiia

Abstract The mechanism of generation of factor VIIa, considered the initiating protease in the tissue factor-initiated extrinsic limb of blood coagulation, is obscure. Decreased levels of plasma VIIa in individuals with congenital factor IX deficiency suggest that generation of VIIa is dependent on an activation product of factor IX. Factor VIIa activates IX to IXa by a two-step removal of the activation peptide with cleavages occurring after R191 and R226. Factor IXaα, however, is IX cleaved only after R226, and not after R191. We tested the hypothesis that IXaα activates VII with mutant IX that could be cleaved only at R226 and thus generate only IXaα upon activation. Factor IXaα demonstrated 1.6% the coagulant activity of IXa in a contact activation-based assay of the intrinsic activation limb and was less efficient than IXa at activating factor X in the presence of factor VIIIa. However, IXaα and IXa had indistinguishable amidolytic activity, and, strikingly, both catalyzed the cleavage required to convert VII to VIIa with indistinguishable kinetic parameters that were augmented by phospholipids, but not by factor VIIIa or tissue factor. We propose that IXa and IXaα participate in a pathway of reciprocal activation of VII and IX that does not require a protein cofactor. Since both VIIa and activated IX are equally plausible as the initiating protease for the extrinsic limb of blood coagulation, it might be appropriate to illustrate this key step of hemostasis as currently being unknown.

scholarly journals The structures of the carbohydrate moieties of bovine blood coagulation factor IX (Christmas factor).

1983 ◽  
Vol 258 (10) ◽  
pp. 6020-6024 ◽  
Author(s):  
T Mizuochi ◽  
T Taniguchi ◽  
K Fujikawa ◽  
K Titani ◽  
A Kobata
Keyword(s):  
Blood Coagulation ◽  
Coagulation Factor ◽  
Factor Ix ◽  
Bovine Blood ◽  
Coagulation Factor Ix

scholarly journals Surface-loop residue Lys316 in blood coagulation Factor IX is a major determinant for Factor X but not antithrombin recognition

2000 ◽  
Vol 350 (3) ◽  
pp. 701-707 ◽  
Author(s):  
Joost A. KOLKMAN ◽  
Koen MERTENS
Keyword(s):  
Blood Coagulation ◽  
Active Site ◽  
Coagulation Factor ◽  
Factor Ix ◽  
Factor X ◽  
Natural Substrate ◽  
Peptide Substrates ◽  
Fold Reduction ◽  
Variable Surface ◽  
Surface Loops

The active site of activated Factor IX (FIXa) and related blood-coagulation enzymes is surrounded by a number of highly variable surface loops, which contribute to the characteristic substrate specificity of each individual enzyme. FIX residue Lys316 is located in one of these loops and mutation of this residue to Glu is associated with haemophilia B. In the present study we investigated the functional role of Lys316 in human FIXa by analysing the purified and activated FIX mutants FIXa-K316E and FIXa-K316A. FIXa-K316E was indistinguishable from normal FIXa in binding the competitive active-site inhibitor p-aminobenzamidine. In addition, substitution of Glu for Lys316 had no significant effect on the reactivity towards various synthetic tripeptide substrates. Inhibition by the macromolecular inhibitor antithrombin was only slightly reduced for both FIXa mutants (less than 2-fold). In contrast, proteolytic activity of FIXa-K316E towards the natural substrate Factor X (FX) was virtually lacking, while the Lys316 to Ala mutation resulted in a more than 10-fold reduction in FX activation. Thus residue Lys316 plays a key role in FIXa activity towards FX. The requirement for Lys at position 316 for FX activation was also evident in the presence of the cofactor activated Factor VIII, although to a lesser extent than in its absence. These data demonstrate that Lys316 specifically determines the reactivity of FIXa towards its natural substrate FX, but not to synthetic peptide substrates or antithrombin.

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