The fibrinogen sequences that interact with thrombin

Abstract

PROTEASE thrombin interacts with a T variety of substrates and as a consequence is involved in a number of physiologic processes. Fibrinogen is a particularly interesting substrate of thrombin for a number of reasons. First, thrombin cleaves not just one but four peptide bonds in fibrinogen, apparently in four successive steps. As a result ofthese proteolytic cleavages, the soluble fibrinogen molecules are converted into an insoluble fibrous polymer. In addition, the affinity of the enzyme for the final product, fibrin, is similar to that for the substrate, fibrinogen. Active thrombin is thus bound by the fibrin clot in a form largely resistant to inactivation by thrombin inhibitors, a situation that has important clinical consequences and complicates clinical anticoagulant therapy.