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La aberración del diastereómero 4S del 4-hidroxiprolina
Matthew D Shoulders1, Frank W Kotch, Amit Choudhary
1Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Journal of the American Chemical Society
|August 5, 2010
Resumen
La configuración de los grupos hidroxilo en los residuos de prolina tiene un impacto crítico en la estructura de las proteínas. La incorporación del diastereómero (2S,4S)-4-hidroxiprolina (hyp) en modelos de colágeno reveló propiedades conformacionales y estabilidad únicas.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Estructural Biología estructural.
- Química de las proteínas química de las proteínas.
Sus antecedentes:
- Las prolyl 4-hidroxilasas modifican los residuos de prolina (Pro) a (2S,4R) -4-hidroxiprolina (Hyp) en proteínas como el colágeno.
- Esta modificación impone un anillo de desgarro C ((gamma) -exo, estabilizando la triple hélice de colágeno.
- El diastereómero (2S,4S)-4-hidroxiprolina (hyp) no se ha observado en las proteínas.
Objetivo del estudio:
- Para investigar los efectos de la incorporación del hip diastereómero en un sistema modelo de colágeno.
- Comprender cómo el hip influye en la estructura y la estabilidad de las proteínas en comparación con el Hyp.
Principales métodos:
- Cálculos de la teoría funcional de la densidad (DFT).
- Espectroscopia y cristalografía.
- Estudios de calorimetría en un sistema modelo de colágeno.
Principales resultados:
- La 4S-hidroxilación de Pro a hip hace que se produzca un anillo endogámico C. pucker.
- Un enlace de hidrógeno transanular en hip distorsiona los ángulos de torsión típicos de la cadena principal y estabiliza el enlace péptido anterior.
- La O-metilación de hip a (2S,4S)-4-metoxiprolina (mop) elimina este enlace de hidrógeno, restaurando un pucker estándar C(gamma) -endo y aumentando la estabilidad de la triple hélice de colágeno.
Conclusiones:
- La configuración estereoquímica de los grupos hidroxilo en los residuos de prolina es crucial para la estructura y la estabilidad de las proteínas.
- El diastereómero hipo confiere propiedades estructurales y conformacionales únicas a los modelos de colágeno.
- Los residuos de Mop mejoran la estabilidad de la triple hélice de colágeno más que los residuos de hip, enfatizando la importancia de la configuración del grupo hidroxilo.
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