Two heads are better than one: crystal structure of the insect derived double domain Kazal inhibitor rhodniin in complex with thrombin
Research article published in The EMBO journal (1995)
Abstract
Rhodniin is a highly specific inhibitor of thrombin isolated from the assassin bug Rhodnius prolixus. The 2.6 Angstrum crystal structure of the non-covalent complex between recombinant rhodniin and bovine alpha-thrombin reveals that the two Kazal-type domains of rhodniin bind to different sites of thrombin. The amino-terminal domain binds in a substrate-like manner to the narrow active-site cleft of thrombin; the imidazole group of the P1 His residue extends into the S1 pocket to form favourable hydrogen/ionic bonds with Asp189 at its bottom, and additionally with Glu192 at its entrance. The carboxy-terminal domain, whose distorted reactive-site loop cannot adopt the canonical conformation, docks to the fibrinogen recognition exosite via extensive electrostatic interactions. The rather acidic polypeptide linking the two domains is displaced from the thrombin surface, with none of its residues involved in direct salt bridges with thrombin. The tight (Ki = 2 x 10(-13) M) binding of rhodniin to thrombin is the result of the sum of steric and charge complementarity of the amino-terminal domain towards the active-site cleft, and of the electrostatic interactions between the carboxy-terminal domain and the exosite.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Rhodniin is a highly specific inhibitor of thrombin isolated from the assassin bug Rhodnius prolixus.
Por qué esto importa para la hirudoterapia
Este artículo reporta la estructura cristalina a 2,6 Å de la rodnina, un inhibidor altamente específico de la trombina proveniente del chinche asesino Rhodnius prolixus, en complejo con alfa-trombina bovina. El resumen describe un inhibidor de dos dominios Kazal cuyo dominio N-terminal se une al sitio activo de manera análoga a un sustrato (P1 His en el bolsillo S1), mientras que el dominio C-terminal se acopla al exosito de reconocimiento del fibrinógeno, generando una unión estrecha (Ki ~2 x 10^-13 M). Para la ASH, esto es relevante como un ejemplo comparativo de inhibición convergente de doble sitio sobre la trombina en un artrópodo hematófago, paralelizando conceptualmente el mecanismo de la hirudina. La advertencia es que no se involucran sanguijuelas ni moléculas derivadas de sanguijuela; la relevancia es únicamente indirecta y comparativa.
Citación
Two heads are better than one: crystal structure of the insect derived double domain Kazal inhibitor rhodniin in complex with thrombin
van de Locht A et al. · The EMBO journal, 1995
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026