Characterization of the kinetic pathway for fibrin promotion of .alpha.-thrombin-catalyzed activation of plasma factor XIII

摘要: Kinetic and thermodynamic studies are presented showing that the cofactor activity of fibrin I (polymerized des-A fibrinogen) in alpha-thrombin-catalyzed proteolysis activation peptide (AP) from plasma factor XIII can be attributed to formation a I-plasma complex (Kd = 65 nM), which is processed by alpha-thrombin more efficiently (kcat/Km 1.2 x 10(7) M-1 s-1) than free, uncomplexed 1.4 10(5) s-1). The increase specificity constant (kcat/Km) shown largely due an apparent affinity for I, as reflected 30-fold decrease Michaelis observed bound relative XIII. Analysis initial rates hydrolysis fibrinopeptide B (FPB) polymer presence indicated ternary alpha-thrombin, XIII, competent catalyze cleavage both FPB AP This observation consistent with view within anchored through binding site distinct active (an exosite) alternatively complexed moiety or I. conclusion supported 12-residue peptide, binds exosite blocks interaction fibrinogen fibrin, competitively inhibits release complex.