[HTML][HTML] Selective disruption of heparin and antithrombin-mediated regulation of human factor IX
PR Westmark, P Tanratana, JP Sheehan - Journal of Thrombosis and …, 2015 - Elsevier
Background Interaction with antithrombin and heparin regulates distribution, activity, and
clearance of factor IXa (FIXa). Hemophilia B prophylaxis targets plasma FIX levels> 1% but
neglects extravascular FIX, which colocalizes with antithrombin–heparan sulfate. Objective
Combined mutagenesis of FIX was undertaken to selectively disrupt heparin-and
antithrombin-mediated regulation of the protease. Methods Human FIX alanine substitutions
in the heparin (K126A and K132A) and antithrombin (R150A) exosites were characterized …
clearance of factor IXa (FIXa). Hemophilia B prophylaxis targets plasma FIX levels> 1% but
neglects extravascular FIX, which colocalizes with antithrombin–heparan sulfate. Objective
Combined mutagenesis of FIX was undertaken to selectively disrupt heparin-and
antithrombin-mediated regulation of the protease. Methods Human FIX alanine substitutions
in the heparin (K126A and K132A) and antithrombin (R150A) exosites were characterized …