The functional role of the autolysis loop in the regulation of factor X upon hemostatic response

摘要: BackgroundThe regulation of factor X (FX) is critical to maintain the balance between blood coagulation and fluidity.ObjectivesTo functionally characterize the role of the FX autolysis loop in the regulation of the zymogen and active form of FX.MethodsWe introduced novel N‐linked glycosylations on the surface‐exposed loop spanning residues 143–150 (chymotrypsin numbering) of FX. The activity and inhibition of recombinant FX variants was quantified in pure component assays. The in vitro thrombin generation potential of the FX variants was evaluated in FX‐depleted plasma.ResultsThe factor VIIa (FVIIa)‐mediated activation and prothrombin activation was reduced, presumably through steric hinderance. Prothrombin activation was, however, recovered in presence of cofactor factor Va (FVa) despite a reduced prothrombinase assembly. The introduced N‐glycans exhibited position‐specific effects on the …