X-ray structure of antistasin at 1.9 A resolution and its modelled complex with blood coagulation factor Xa
Research article published in EMBO Journal (1997)
Abstract
The three-dimensional structure of antistasin, a potent inhibitor of blood coagulation factor Xa, from the Mexican leech Haementeria officinalis was determined at 1.9 A resolution by X-ray crystallography. The structure reveals a novel protein fold composed of two homologous domains, each resembling the structure of hirustasin, a related 55-residue protease inhibitor. However, hirustasin has a different overall shape than the individual antistasin domains, it contains four rather than two beta-strands, and does not inhibit factor Xa. The two antistasin domains can be subdivided into two similarly sized subdomains with different relative orientations. Consequently, the domain shapes are different, the N-terminal domain being wedge-shaped and the C-terminal domain flat. Docking studies suggest that differences in domain shape enable the N-terminal, but not C-terminal, domain of antistasin to bind and inhibit factor Xa, even though both have a very similar reactive site. Furthermore, a putative exosite binding region could be defined in the N-terminal domain of antistasin, comprising residues 15-17, which is likely to interact with a cluster of positively charged residues on the factor Xa surface (Arg222/Lys223/Lys224). This exosite binding region explains the specificity and inhibitory potency of antistasin towards factor Xa. In the C-terminal domain of antistasin, these exosite interactions are prevented due to the different overall shape of this domain.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
X-ray structure of antistasin at 1.9 A resolution and its modelled complex with blood coagulation factor Xa.
Por qué esto importa para la hirudoterapia
Este estudio determinó la estructura cristalina de rayos X a 1,9 Å de la antistasina, un potente inhibidor del factor Xa de la sanguijuela mexicana Haementeria officinalis, y modelizó su complejo con el factor Xa. La estructura revela dos dominios homólogos; los estudios de acoplamiento sugieren que el dominio N-terminal (con forma de cuña) puede unirse e inhibir al factor Xa a través de una región de exositio definida, mientras que el dominio C-terminal plano no puede hacerlo a pesar de presentar un sitio reactivo similar. Esto es relevante para la ASH como estudio de estructura-función de un anticoagulante derivado de sanguijuela. Advertencia: los hallazgos son estructurales/computacionales (complejo modelizado) sin validación in vivo ni clínica.
Citación
X-ray structure of antistasin at 1.9 A resolution and its modelled complex with blood coagulation factor Xa
Lapatto R et al. · EMBO Journal, 1997
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026