Ecarin

This chapter describes the structural chemistry and the biological aspects of Ecarin. Early work describes ecarin as being fibrinogenolytic; however, when purified to homogeneity, the enzyme showed strict substrate specificity for prothrombin and no fibrinogenolytic activity. Ecarin is a single-chain glycoprotein of around 55 kDa, pI 4.5. Higher molecular masses of 72 kDa and 84–86 kDa have been reported, possibly reflecting differences in glycosylation, post-translational processing or subspecies differences. A signal sequence and propeptide sequence are found in the cDNA sequence, indicating that ecarin is synthesized as a zymogen molecule. The enzyme is a class III reprolysin comprising a metalloprotease and a disintegrin domain. In the disintegrin domain, the Arg-Gly-Asp (RGD) sequence is replaced by Arg-Asp-Asp and there is strong sequence homology with other members of the reprolysin subfamily. Ecarin plays an important role with respect to the coagulation defects associated with Echis envenomation. In humans, incoagulable blood following bites by Echis is associated with defibrination and a decrease in clotting factors as a result of prothrombin activation.