Introduction

Thrombin has central bioregulatory functions in hemostasis.' Some 30 years ago, thrombin was shown to function as a highly selective proteolytic enzyme in the clotting of fibrinogen solutions? It was also found to be an esterolytically active enzyme: and relative to this activity, its clotting activity could be differentially lost by chemical modification' or by autoproteolytic degradation.' More recently, thrombin has also been demonstrated to function nonenzymically, or hormonally, in the stimulation of specific cellular activities. Both enzymic and nonenzymic mechanisms are required for the initiation of fibroblast proliferation.' The development of our understanding of thrombin functions has paralleled our understanding of its structure, which in turn has depended on the availability of methods and material. Bovine thrombin became available in large amounts through advances made at Wayne State University,' and human thrombin by members of the same group who had moved to Albany?" The amino acid sequence of bovine prothrombin was determined in Denmark," that of human prothrombin by contributions from three groups.''-14 The genes for the two prothrombins were subsequently sequenced in Seattle.'"."' Although crystals of bovine thrombin were grown more than a decade ago," the crystallographic structure is not yet available. Three-dimensional models have been deduced for the thrombin B chain based on its homology with chymotrypsin." In addition to the catalytic site, the enzymic form with high clotting activity (a-thrombin) has an important exosite involved in fibrin(ogen) interactions and other biological activities.lq