Thrombin: structural features related to specificity.

A comparison of the primary structure of human thrombin with the structures of chymotrypsin, trypsin, elastase and factor Xabeta reveals several structural features which may be involved in the specificity of thrombin toward macromolecular substrates. Among the major structural differences noted in such a comparison are the insertions of five extended peptide regions in the primary structure of alpha-thrombin when compared to chymotrypsin. These insertions, which we refer to as "loops", have been designated A, B, C, D, and E. The A, B and C "loops" in human thrombin appear to be large enough to interact at or near the active active site if an alpha-thrombin-chymotrypsin three-dimensional structural homology is assumed. In beta-thrombin, the configuration of the A and B "loops" may be perturbed by proteolysis, and the ability of beta-thrombin to clot fibrinogen is thus reduced. Perturbation of the configuration of the C "loops" by proteolysis in the formation of gamma-thrombin may further reduce the ability of thrombin to bind fibrinogen.