JOHN PATRICK SHEEHAN
Affiliation: University of Wisconsin
- Heparin inhibits the intrinsic tenase complex by interacting with an exosite on factor IXaJohn P Sheehan
Department of Medicine Hematology, University of Wisconsin Madison, 53706, USA
Biochemistry 42:11316-25. 2003..This exosite may contribute to the clinical efficacy of heparin and represents a novel target for antithrombotic therapy...
- Depolymerized holothurian glycosaminoglycan and heparin inhibit the intrinsic tenase complex by a common antithrombin-independent mechanismJohn P Sheehan
Department of Medicine Hematology, University of Wisconsin, Medical Sciences Center Rm 4285, 1300 University Avenue, Madison, WI 53706, USA
Blood 107:3876-82. 2006..DHG also accelerated decay of the intact intrinsic tenase complex. Thus, DHG binds to an exosite on factor IXa that overlaps with the binding sites for LMWH and factor VIIIa, disrupting critical factor IXa-factor VIIIa interactions...
- The factor IXa heparin-binding exosite is a cofactor interactive site: mechanism for antithrombin-independent inhibition of intrinsic tenase by heparinQiu Ping Yuan
Department of Medicine Hematology, University of Wisconsin Madison, Madison, Wisconsin 53706, USA
Biochemistry 44:3615-25. 2005..Thus, LMWH inhibits intrinsic tenase by interacting with the heparin-binding exosite in the factor IXa protease domain, which disrupts interaction with the factor VIIIa A2 domain...
- The heparin-binding exosite is critical to allosteric activation of factor IXa in the intrinsic tenase complex: the role of arginine 165 and factor XTina M Misenheimer
University of Wisconsin Madison, Department of Medicine Hematology Oncology, Madison, Wisconsin 53706, USA
Biochemistry 46:7886-95. 2007..These results suggest that the factor IXa heparin-binding exosite participates in both cofactor binding and protease activation, and cofactor affinity is linked to active site conformation and factor X interaction during enzyme assembly...
- Fucosylated chondroitin sulfate inhibits plasma thrombin generation via targeting of the factor IXa heparin-binding exositeYang Buyue
Department of Medicine Hematology Oncology, University of Wisconsin Madison, Madison, WI 53706, USA
Blood 114:3092-100. 2009..Glycosaminoglycan-mediated intrinsic tenase inhibition is a novel antithrombotic mechanism with physiologic and therapeutic applications...
- The regulation of factor IXa by supersulfated low molecular weight heparinTina M Misenheimer
Department of Medicine Hematology Oncology, University of Wisconsin Madison, Madison, Wisconsin 53706, United States
Biochemistry 49:9997-10005. 2010..An extensive overlap exists between the heparin and factor VIIIa binding sites on the protease domain, with residues K126 and R233 dominating the heparin interaction and R165 dominating the cofactor interaction...
- The heparin-binding exosite of factor IXa is a critical regulator of plasma thrombin generation and venous thrombosisYang Buyue
Departments of Medicine Hematology Oncology and Pathology, University of Wisconsin Madison, USA
Blood 112:3234-41. 2008..7 minutes, 9.1 minutes (P </= .003), and more than 45 minutes. These data support the role of the factor IXa heparin-binding exosite as a critical regulator of coagulation and novel antithrombotic target...
- Physiologic and Pharmacologic Regulation of Factor IXaJohn Sheehan; Fiscal Year: 2009..Finally, these studies will provide proof of principle for this exosite as a critical therapeutic target, and identify lead compounds for a novel class of antithrombotics. ..