Recombinant decorsin: dynamics of the RGD recognition site
Research article published in Protein science : a publication of the Protein Society (2000)
Abstract
Decorsin is an antagonist of integrin alphaIIbbeta3 and a potent platelet aggregation inhibitor. A synthetic gene encoding decorsin, originally isolated from the leech Macrobdella decora, was designed, constructed, and expressed in Escherichia coli. The synthetic gene was fused to the stII signal sequence and expressed under the transcriptional control of the E. coli alkaline phosphatase promoter. The protein was purified by size-exclusion filtration of the periplasmic contents followed by reversed-phase high-performance liquid chromatography. Purified recombinant decorsin was found to be indistinguishable from leech-derived decorsin based on amino acid composition, mass spectral analysis, and biological activity assays. Complete sequential assignments of 1H and proton bound 13C resonances were established. Stereospecific assignments of 21 of 25 nondegenerate b-methylene groups were determined. The RGD adhesion site recognized by integrin receptors was found at the apex of a most exposed hairpin loop. The dynamic behavior of decorsin was analyzed using several independent NMR parameters. Although the loop containing the RGD sequence is the most flexible one in decorsin, the conformation of the RGD site itself is more restricted than in other proteins with similar activities.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Decorsin is an antagonist of integrin alphaIIbbeta3 and a potent platelet aggregation inhibitor.
Por qué esto importa para la hirudoterapia
Este estudio describe la expresión recombinante, la purificación y la caracterización estructural mediante RMN de la decorsina, un potente antagonista de la integrina αIIbβ3 e inhibidor de la agregación plaquetaria aislado originalmente de la sanguijuela Macrobdella decora. Se expresó un gen sintético en E. coli, y se confirmó que la proteína recombinante era indistinguible de la decorsina derivada de sanguijuela en composición, masa y bioactividad. El sitio de reconocimiento RGD se localizó en el vértice de un bucle en horquilla expuesto y flexible, aunque la conformación del RGD en sí estaba más restringida que en proteínas comparables. Este trabajo es directamente relevante para el ámbito de ASH, ya que amplía la comprensión estructural de una proteína antitrombótica secretada por la sanguijuela y valida la producción recombinante. El estudio es puramente biofísico/bioquímico, sin datos in vivo ni clínicos.
Citación
Recombinant decorsin: dynamics of the RGD recognition site
Krezel AM et al. · Protein science : a publication of the Protein Society, 2000
Contexto clínico relacionado
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026