Activation mechanisms of coagulation factor IX.
Blood haemostasis is accomplished by a complex network of coagulatory and fibrinolytic processes. These processes have to be delicately balanced, as clinically manifested by bleeding disorders, such as haemophilia A and B. These disorders are caused by defects in coagulation factor VIII and factor IX, respectively. Following a dual strategy, we emphasise on the one hand principles conserved in most coagulation enzymes, thus mirroring much of the underlying complexity in haemostasis; on the other hand, we identify enzymatic properties of the factor IXa-factor VIIIa system (Xase) that distinguish this proteolytic machine from other components of the coagulation system. While the exact mechanisms of its activity modulation remain baffling until today, superactive factor IX mutants significantly improve our current understanding and serve as a specific and testable model of Xase action.
Zögg
Thomas
T
Department of Molecular Biology, Division of Structural Biology, University of Salzburg, Billrothstrasse 11, A-5020 Salzburg, Austria.
Brandstetter
Hans
H
D000818:Animals; D001777:Blood Coagulation; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation; D005164:Factor IX / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D015949:Factor IXa / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D009363:Neoplasm Proteins; D005164:Factor IX; D015949:Factor IXa; D003546:Cysteine Endopeptidases; C030910:cancer procoagulant