Anticoagulant dysfunction of human Arg352Trp-activated protein C caused by defective factor Va inactivation.

摘要: The dysfunctional mutant R352W-protein C was found in two patients with venous thrombosis. R352A-protein constructed to define the contribution of charge/size residue at 352 on protein (chymotrypsin numbering 187). Compared wild type-protein C, showed no difference activation by thrombin-thrombomodulin or alpha-thrombin. However, R352W-activated (APC) anticoagulant activity (aPTT assay) reduced approximately 65%. Although catalytic efficiency R352W-APC towards oligopeptide substrate S-2366 unperturbed, factor Va and R506Q-factor were not efficiently inactivated compared type-APC. R352A-APC inactivation VIIIa-inactivation presence S. These observations suggest that dysfunction may be one mechanisms leading thrombosis affected R352 plays an important role physiological functioning APC.