title: Molecular Interactions of Thrombin.
abstract: Thrombin possesses at least three independent binding sites for substrate, inhibitor, and co-factor molecules, four counting the Na+ ion binding site. The S1 subsite of the active site is specific for an arginine side group, while S2 is a more extended apolar site. The highly electropositive S' subsites of the fibrinogen exosite circumnavigate about a third of the thrombin surface, although evidence suggests molecular recognition of a tetra- or pentapeptide sequence is sufficient for binding. Another highly electropositive region of thrombin that binds the second kringle of prothrombin is the heparin binding site. All three of these sites display distinct binding modes with different molecules. These can arise from tolerance of imprecision of binding and/or from reversal of ligand main chain direction in active site and fibrinogen exosite binding. Preliminary indications suggest similar principles may apply to the heparin site. Such varied behavior easily accounts for the diversity of thrombin functions at the molecular level. The complexity of the behavior is compounded even more by a Na+ ion binding site that produces a procoagulant fast form of thrombin. The slow form (in the absence of Na+ ion) is anticoagulant.
authors.affiliation: Dept. of Chemistry, Michigan State University, East Lansing 48824-1322, USA.
authors.forename: A
authors.initials: A
authors.lastname: Tulinsky
mesh_terms: D001665:Binding Sites; D001777:Blood Coagulation; D006801:Humans; D011487:Protein Conformation; D017510:Protein Folding; D013917:Thrombin / Q000737:chemistry / Q000502:physiology*
chemical_list: D013917:Thrombin