Antithrombin- and Heparin-Binding Exosites Regulate Extravascular Binding and Clearance of Factor IXa
نویسندگان
چکیده
منابع مشابه
Localization of the heparin binding exosite of factor IXa.
Factor IXa (FIXa) is known to have a binding site for heparin that has not been mapped by a mutagenesis study. By homology modeling based on structural data, we identified eight basic residues in the catalytic domain of FIXa that can potentially bind to heparin. These residues, Lys(98), Lys(126), Arg(165), Arg(170), Lys(173), Lys(230), Arg(233), and Lys(239) (chymotrypsin numbering) were substi...
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We investigated the kinetics of the inhibitory action of antithrombin III and antithrombin III plus heparin during the activation of factor X by factor IXa. Generation and inactivation curves were fitted to a three-parameter two-exponentional model to determine the pseudo first-order rate constants of inhibition of factor IXa and factor Xa by antithrombin III/heparin. In the absence of heparin,...
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Products obtained by partial depolymerization of pig mucosal heparin with nitrous acid were fractionated by affinity chromatography on immobilized antithrombin. A high affinity octasaccharide fraction was recovered and reduced with sodium [3H]borohydride, yielding terminal 2,5-anhydro-~-[l-~H]mannitol residues. Partial N-desulfation of this material by treatment with aqueous dimethylsulfoxide r...
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A chromogenic assay for use as a screening test for the identification of antithrombin deficiency is described. The heparin concentration and the incubation time in the assay were optimised specifically to permit the detection of heparin binding defects of antithrombin. The sensitivity of antithrombin assays for the detection of this type of variant was significantly impaired when an incubation...
متن کاملBinding of factor VIIa to tissue factor permits rapid antithrombin III/heparin inhibition of factor VIIa.
Because free factor VIIa is inactivated only very slowly by a plasma concentration of antithrombin III (AT III) even in the presence of heparin, it has been assumed that AT III plays no significant role in regulating the initiation of tissue factor-dependent blood coagulation. However, in the present study, we present evidence that factor VIIa bound to tissue factor, unlike free factor VIIa, is...
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ژورنال
عنوان ژورنال: Blood
سال: 2019
ISSN: 0006-4971,1528-0020
DOI: 10.1182/blood-2019-131580