Mapping active sites of blood coagulation serine proteases--activated protein C and thrombin--on simple graphics...

Employing the known three-dimensional (3D) structure of trypsin, we constructed simple graphics models of human-activated protein C and thrombin catalytic domains. Considering the structural analysis of bovine trypsin and pancreatic trypsin inhibitor complex, the difference of active-site amino acid sequences of human protein C inhibitor and antithrombin III and their inhibitory selectivity toward activated protein C and thrombin, we estimated the enzymatic subsites of activated protein C and thrombin and mapped them on the graphics models. Predicted favorable contacts can explain substrate selectivity of the enzymes. In this study, we used two types of modified ALPHA representations extensively. Since almost no report on the 3D structure of a blood coagulation factor has appeared and even an extensive molecular mechanics or dynamics calculation cannot produce satisfying results, simple graphics representation has several advantages.