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Inesperadamente rápida isomerización cis/trans de los enlaces péptidos Xaa-Pro en péptidos cíclicos con restricción
Tiesheng Shi1, Stephen M Spain, Dallas L Rabenstein
1Department of Chemistry, University of California, Riverside, California 92521, USA.
Journal of the American Chemical Society
|January 22, 2004
Resumen
Los enlaces cíclicos de disulfuro en los péptidos inesperadamente aceleran la isomerización cis-trans, lo que sugiere una catálisis intramolecular. Este hallazgo ofrece información sobre la flexibilidad conformacional de los sitios activos de la enzima oxidorreductaza.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Química Biología química.
- Biología Estructural Biología estructural.
Sus antecedentes:
- La isomerización del enlace péptido es crucial para la función de las proteínas.
- Los residuos de prolina influyen significativamente en la conformación y dinámica de la columna vertebral del péptido.
- La superfamilia de la tioredoxina de las enzimas oxidorreductasas juega un papel vital en la regulación redox.
Objetivo del estudio:
- Para sintetizar y caracterizar el disulfuro cíclico y los péptidos dicilo acíclicos.
- Para investigar la cinética de la isomerización cis-trans a través de enlaces péptidos que involucran prolina.
- Explorar el impacto de las restricciones de los enlaces disulfuro en las tasas y mecanismos de isomerización.
Principales métodos:
- Síntesis y caracterización de péptidos mediante espectrometría de masas y espectroscopia de RMN.
- Determinación de las constantes de velocidad de isomerización cis-trans y trans-cis (kct y ktc) mediante RMN de transferencia de magnetización.
- Análisis de las constantes de velocidad dependientes de la temperatura para obtener parámetros de activación.
Principales resultados:
- Sintetizó y caracterizó varios péptidos de disulfuro cíclico y dietiol acíclico.
- Las tasas de isomerización cis/trans cuantificadas a través de los enlaces péptidos Cys-Pro y Gly-Pro.
- Se observaron mejoras en la tasa de isomerización cis/trans en péptidos disulfuro cíclicos (factor de 2-13) en comparación con las formas acíclicas.
- Propuso un mecanismo de catálisis intramolecular que involucra enlaces de hidrógeno en el estado de transición.
Conclusiones:
- Las restricciones del enlace disulfuro mejoran las tasas de isomerización cis/trans, lo que indica una inusual flexibilidad conformacional.
- Los hallazgos sugieren un nuevo mecanismo de catálisis intramolecular para la isomerización de enlaces péptidos.
- Estos péptidos modelo proporcionan información sobre la dinámica del sitio activo de las enzimas oxidadas de la superfamilia de la tioredoxina.
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