Determinants of specificity of factor xa interaction with its physiological inhibitors.
Review published in Mini reviews in medicinal chemistry (2006)
Abstract
Factor Xa (fXa) is the vitamin K-dependent serine protease of the prothrombinase complex (fXa, factor Va, negatively charged membrane, and calcium) which is responsible for the conversion of prothrombin to thrombin in the final stage of the coagulation cascade. The proteolytic activity of fXa in plasma is primarily regulated by three physiological inhibitors, antithrombin (AT), protein Z-dependent protease inhibitor (ZPI) and tissue factor pathway inhibitor (TFPI). The first two inhibitors belong to the serpin family of plasma inhibitors, both of which require cofactors for their effective interaction with fXa. Thus, the AT interaction with the heparin-like glycosaminoglycans on the surface of the endothelium, and the ZPI complex formation with protein Z on membrane phospholipids is required for the physiological regulation of fXa by both serpins. On the other hand, TFPI is a slow and tight-binding, Kunitz type inhibitor that is capable of rapidly inhibiting fXa independent of a cofactor. This article will review the structural features that enable fXa to specifically interact with these three inhibitors under different conditions.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Factor Xa (fXa) is the vitamin K-dependent serine protease of the prothrombinase complex (fXa, factor Va, negatively charged membrane, and calcium) which is responsible for the conversion of prothrombin to thrombin in the final stage of the coagulation cascade. The proteolytic activity of fXa in...
Por qué esto importa para la hirudoterapia
Esta revisión analiza las características estructurales que determinan la especificidad de las interacciones del factor Xa con sus tres principales inhibidores fisiológicos: la antitrombina, el inhibidor de proteasa dependiente de proteína Z y el inhibidor de la vía del factor tisular (TFPI). Examina los mecanismos diferenciados de estos inhibidores, señalando que, mientras los dos primeros requieren cofactores específicos para regular al factor Xa, el TFPI actúa como un inhibidor de tipo Kunitz que funciona con independencia de un cofactor. Si bien la comprensión de estos mecanismos reguladores fisiológicos resulta crucial para la investigación anticoagulante general, el artículo no aborda la hirudoterapia ni el secretoma de la sanguijuela. No se mencionan las sanguijuelas, la hirudina ni otros anticoagulantes derivados de la sanguijuela, lo que hace que su relevancia para la American Society of Hirudotherapy sea puramente indirecta.
Citación
Determinants of specificity of factor xa interaction with its physiological inhibitors.
Rezaie · Mini reviews in medicinal chemistry, 2006
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Añadido a la biblioteca ASH: May 28, 2026 · Última actualización del sitio: 18 de junio de 2026