La hidrofobia del sitio activo y la evolución convergente de la actividad de la paraoxonas en enzimas estructuralmente divergentes: el caso de la paraoxonas sérica 1
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Ver abstracta en PubMed
Resumen
Este resumen es generado por máquina.Las variantes de la paraoxonasa sérica 1 (PON1) en Tyr71 tienen un impacto mínimo en la actividad de la lactonasa, pero reducen significativamente la actividad de la organofosfatasa. La modulación de la hidrofobidad del sitio activo es clave para el diseño de nuevas hidrolasas organofosforadas.
Área De La Ciencia
- La bioquímica
- Enzimología
- Biología estructural
Sus Antecedentes
- La paraoxonasa sérica 1 (PON1) es una enzima versátil con actividades de lactonasa y organofosfatasa.
- PON1 presenta un bucle flexible (residuos 70-81) que cubre su sitio activo, incluido un residuo crítico Tyr71.
Objetivo Del Estudio
- Investigar el papel de las variantes de Tyr71 en la estabilidad del sitio activo y las funciones catalíticas de PON1.
- Comprender cómo las sustituciones de Y71 afectan las actividades de lactonasas y organofosfatasas de PON1.
Principales Métodos
- Análisis experimentales y computacionales de las variantes de Y71 en PON1.
- Evaluar los cambios en la forma del sitio activo, el volumen, la flexibilidad del bucle y la accesibilidad al solvente.
- Comparando PON1 con otras organofosfatasas.
Principales Resultados
- Las sustituciones de Y71 tuvieron un impacto mínimo en la actividad de la lactonasa de PON1.
- La actividad de la organofosfatasa (kcat) se redujo hasta 100 veces por sustituciones de Y71.
- Las sustituciones expandieron el volumen del sitio activo, aumentando la accesibilidad al agua, particularmente para la actividad de la organofosfatasa.
Conclusiones
- La modulación de la hidrofobidad del sitio activo es crucial para la evolución de la actividad de la organofosfatasa.
- La actividad organofosfatasa de PON1 es más sensible a las mutaciones de Y71 que su actividad lactonasa.
- Los hallazgos pueden orientar el diseño racional de nuevas hidrolasas organofosforadas.
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