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
This review analyzes the structural features that determine the specificity of factor Xa interactions with its three primary physiological inhibitors: antithrombin, protein Z-dependent protease inhibitor, and tissue factor pathway inhibitor (TFPI). It discusses the distinct mechanisms of these inhibitors, noting that while the first two require specific cofactors to regulate factor Xa, TFPI acts as a Kunitz-type inhibitor that functions independently of a cofactor. While understanding these physiological regulatory mechanisms is crucial for general anticoagulant research, the article does not discuss hirudotherapy or the leech secretome. There is no mention of leeches, hirudin, or other leech-derived anticoagulants, making its relevance to the American Society of Hirudotherapy purely indirect.
Citación
Determinants of specificity of factor xa interaction with its physiological inhibitors.
Rezaie · Mini reviews in medicinal chemistry, 2006
Contexto clínico relacionado
Explore cómo esta investigación se conecta con la práctica clínica
Añadido a la biblioteca ASH: May 28, 2026 · Última actualización del sitio: June 18, 2026