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  • Title: [Regulation of alpha and beta/gamma-thrombin activity by heparin and indole].
    Author: Strukova SM, Semenova OA, Kireeva EG.
    Journal: Biokhimiia; 1980 Apr; 45(4):738-46. PubMed ID: 7378498.
    Abstract:
    Indole was shown to stimulate TAME hydrolysis by alpha-thrombin with KA=7,7 mM, alpha=0,55, beta=1,5 and that by beta/gamma-thrombin with KA=9,5 mM, alpha=0,47 and beta=2,08. Indole promotes both the formation and transformation of the enzyme-substrate complex. No effect of substrate activation was observed in the presence of indole, which suggests the identity of the binding sites of indole and the added TAME molecule. Heparin was shown to form an equimolar stoicheometric complex with both alpha- and beta/gamma-thrombin, which results in 40% inhibition of the TAME-esterase, clotting and prothrombinolytic activities of alpha-thrombin and 25% and 40% inhibition of the TAME-esterase and prothrombinolytic activity of beta/gamma-thrombin, respectively. The fact that alpha- and beta/gamma-thrombin partially retain their catalytic properties even at a 5-fold molar excess of the inhibitor indicates that heparin binds to the thrombin molecule at a site other than the active center. Heparin does not prevent the effect of substrate activation at high TAME concentrations. This finding suggests that the localization of binding sites of heparin and the added TAME molecule (and, therefore, indole) in the thrombin molecule is different.
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