Mutational analysis of antistasin, an inhibitor of blood coagulation factor Xa derived from the Mexican leech Haementeria officinalis
Research article published in Thrombosis research (1994)
Abstract
Antistasin is a Factor Xa inhibitor that is present in the salivary glands of the Mexican leech Haementeria officinalis. The antistasin protein consists of 119 amino acids, of which residues 1-55 (domain I) are 56% similar to residues 56-110 (domain II). Of the nine C-terminal amino acids (residues 111-119; domain III), four are positively charged. The reactive site for Factor Xa is located in domain I. In this study we assessed the role of separate domains and of individual amino acids in the reactive site for the inhibition of Factor Xa. A series of mutants was constructed and expressed in Chinese hamster ovary (CHO) cells. In vitro chromogenic assays for Factor Xa show that domain I is sufficient for inhibition of Factor Xa. Domains II and III neither contain any intrinsic Factor Xa inhibitory activity, nor contribute to the activity of domain I. Furthermore, domain II does not become a Factor Xa inhibitor by partially adaptating its sequence towards that of the reactive site in domain I. Mutation of the cysteine at position 33 is not crucial for Factor Xa inhibition, suggesting a relatively rigid reactive site loop structure.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Mutational analysis of antistasin, an inhibitor of blood coagulation factor Xa derived from the Mexican leech Haementeria officinalis.
Por qué esto importa para la hirudoterapia
Este estudio realizó un análisis mutacional de la antistasina, un inhibidor del factor Xa procedente de las glándulas salivales de la sanguijuela mexicana Haementeria officinalis, mediante la expresión de mutantes de dominio y mutantes puntuales en células CHO. Los ensayos cromogénicos in vitro demostraron que el dominio I (residuos 1–55) por sí solo es suficiente para la inhibición del factor Xa, mientras que los dominios II y III no aportan actividad intrínseca, y la mutación de la cisteína-33 no resulta crucial, lo que sugiere un bucle del sitio reactivo relativamente rígido. Esto es relevante para la ASH como un estudio de estructura-función de un anticoagulante del secretoma de sanguijuela. Matiz honesto: el trabajo es enteramente in vitro, empleando proteína recombinante en cultivo celular, sin datos animales ni clínicos.
Citación
Mutational analysis of antistasin, an inhibitor of blood coagulation factor Xa derived from the Mexican leech Haementeria officinalis
Theunissen HJ et al. · Thrombosis research, 1994
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026