Zymogen binding

Abstract: Factor X is a zymogen in the blood coagulation system which is activated by the serine protease, factor IXa, in a reaction that is promoted by the presence of stimulated platelets. We have shown previously that platelets possess a binding site for factor IXa, the occupancy of which is correlated with the rate of factor X activation (Ahmad et al., 1989b,c). Similarly, we have described a different binding site on the surface of activated platelets to which the substrate for this reaction, factor X, can bind (see the accompanying paper). This “zymogen binding site” is of moderate affinity and is relatively nonspecific; apparently shared to some degree by factor X and other vitamin K-dependent proteins, most notably prothrombin. We have found that prothrombin fragment 1 not only is able to displace factor X from this platelet binding site but also possesses the ability to inhibit the platelet-dependent activation of factor X. We have developed two mathematical models for the activation of factor X by platele...

Abstract: High molecular weight kininogen is a multifunctional plasma protein. After cleavage of bradykinin, the light chain contains a zymogen binding domain (D6), which binds prekallikrein, and a surface binding domain (DS). Using peptides, monoclonal antibodies and deletion mutagenesis, two subdomains, HK-rich and HGK-rich, have been defined as necessary for binding to anionic surfaces and coagulant activity. The heavy chain contains D5, responsible for calpain inhibition. Using &ity labeling, we have shown that the motif QWAG is necessary as a binding domain on HK, but appears to require additional inhibitory sequences to interact With the thiol in the active site of calpain.