Cofactor competition for exosites. The exosite interactions between thrombin and (A) fibrin, (B) thrombomodulin, (C) GpIbα, and (D) heparin have been revealed by recent crystallographic structures. The surface of thrombin is oriented identically in panelsA and B to highlight exosite I, and in panels C and D for exosite II, and the contact surfaces are colored red. It is clear from the stereo depictions that cofactors fibrin (E fragment) and thrombomodulin (EGF domains 5 and 6) share a single binding site on exosite I, and similarly, GpIbα and heparin share a common site on exosite II.