Isolation and characterization of hirustasin, an antistasin-type serine-proteinase inhibitor from the medical leech Hirudo medicinalis
Comparative study published in Eur J Biochem (1994)
Abstract
Antistasin, a potent inhibitor of the blood coagulation factor Xa, is the prototype of a novel family of serine-proteinase inhibitors. We have now isolated, sequenced and characterized an antistasin-type inhibitor from the medical leech Hirudo medicinalis. Hirustasin (Hirudo antistasin) was purified to apparent homogeneity by cation-exchange and affinity chromatography. Amino acid sequencing of the 55 amino acid protein (M(r) 5866) revealed that hirustasin is the only antistasin-type protein known to consist of one domain only; 27% and 32% sequence identity was found to the first and second domains of antistasin, respectively, and a nearly exact conservation of the spacing of the ten cysteine residues. Hirustasin is the first inhibitor of tissue kallikrein identified in leeches, and is also a tight-binding inhibitor of trypsin, chymotrypsin and neutrophil cathepsin G. However, despite the high similarity to antistasin, particularly in the vicinity of the putative reactive-site peptide bond, hirustasin neither inhibits blood coagulation in vitro nor amidolytic activity of isolated factor Xa. Thus, structural elements other than the reactive site sequence significantly influence the specificity of antistasin-type proteinase inhibitors.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Antistasin, a potent inhibitor of the blood coagulation factor Xa, is the prototype of a novel family of serine-proteinase inhibitors.
Por qué esto importa para la hirudoterapia
Este estudio describe el aislamiento, purificación, secuenciación y caracterización bioquímica de la hirustasina, un inhibidor de serina-proteasas de tipo antistasina de 55 aminoácidos aislado de Hirudo medicinalis. La hirustasina es notable por ser el único inhibidor de tipo antistasina de un solo dominio conocido y el primer inhibidor derivado de sanguijuela identificado de la calicreína tisular; también inhibe con firmeza la tripsina, la quimotripsina y la catepsina G de neutrófilos, pero, a pesar de la elevada similitud de secuencia con la antistasina —incluido el espaciado de cisteínas casi conservado—, no inhibe el factor Xa ni la coagulación sanguínea in vitro. Este trabajo es relevante para el ámbito de ASH, ya que amplía el catálogo de inhibidores de serina-proteasas bioactivos del secretoma de la sanguijuela medicinal e ilustra cómo la similitud estructural no predice necesariamente la especificidad funcional. La advertencia honesta es que se trata de un estudio de caracterización bioquímica sin datos in vivo, animales ni clínicos, y el resumen no formula afirmaciones terapéuticas ni de eficacia.
Citación
Isolation and characterization of hirustasin, an antistasin-type serine-proteinase inhibitor from the medical leech Hirudo medicinalis.
Söllner C et al. · Eur J Biochem, 1994
Contexto clínico relacionado
Explore cómo esta investigación se conecta con la práctica clínica
Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026