Refined 1.2 Å crystal structure of the complex formed between subtilisin Carlsberg and the inhibitor eglin c
Structural biology article published in EMBO Journal (1986)
Abstract
The crystal structure of the complex formed between eglin c, an elastase inhibitor from the medical leech, and subtilisin Carlsberg has been determined at 1.2 A resolution by a combination of Patterson search methods and isomorphous replacement techniques. The structure has been refined to a crystallographic R-value of 0.18 (8-1.2 A). Eglin consists of a four-stranded beta-sheet with an alpha-helical segment and the protease-binding loop fixed on opposite sides. This loop, which contains the reactive site Leu45I--Asp46I, is mainly held in its conformation by unique electrostatic/hydrogen bond interactions of Thr44I and Asp46I with the side chains of Arg53I and Arg51I which protrude from the hydrophobic core of the molecule. The conformation around the reactive site is similar to that found in other proteinase inhibitors. The nine residues of the binding loop Gly40I--Arg48I are involved in direct contacts with subtilisin. In this interaction, eglin segment Pro42I--Thr44I forms a three-stranded anti-parallel beta-sheet with subtilisin segments Gly100--Gly102 and Ser125--Gly127. The reactive site peptide bond of eglin is intact, and Ser221 OG of the enzyme is 2.81 A apart from the carbonyl carbon.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
1.2 Å crystal structure of the subtilisin Carlsberg-eglin C complex shows leech eglin C as a four-stranded β-sheet with α-helix and protease-binding loop forming a three-stranded antiparallel β-sheet with subtilisin.
Por qué esto importa para la hirudoterapia
Este estudio determinó la estructura cristalina refinada por rayos X a una resolución de 1.2 Å del complejo entre la eglina c —un inhibidor de elastasa de la sanguijuela medicinal— y la subtilisina Carlsberg, utilizando métodos de búsqueda de Patterson y reemplazo isomorfo (valor R 0.18). La estructura muestra la eglina c como una lámina beta de cuatro hebras con un segmento helicoidal alfa y un bucle de unión a proteasa (sitio reactivo Leu45I-Asp46I) mantenido por interacciones electrostáticas y de puente de hidrógeno, con nueve residuos del bucle contactando a la subtilisina para formar una lámina beta antiparalela de tres hebras; el enlace peptídico del sitio reactivo permanece intacto. Esto es relevante para el dominio de ASH como caracterización estructural de alta resolución de un inhibidor de proteasa del secretoma de la sanguijuela. Advertencia: este es un estudio puramente estructural (cristalografía de rayos X) y no ofrece datos terapéuticos, in vivo ni de hirudoterapia.
Citación
Refined 1.2 Å crystal structure of the complex formed between subtilisin Carlsberg and the inhibitor eglin c.
Bode W, Papamokos E, Musil D, Seemueller U, Fritz H · The EMBO journal, 1986
Contexto clínico relacionado
Explore cómo esta investigación se conecta con la práctica clínica
Añadido a la biblioteca ASH: May 26, 2026 · Última actualización del sitio: 18 de junio de 2026