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Coordinación modificada del sitio activo en una mutante clínica de la sulfitooxidasa
Christian J Doonan1, Heather L Wilson, K V Rajagopalan
1Department of Geological Sciences, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Journal of the American Chemical Society
|July 5, 2007
Resumen
La enzima mutante de la sulfito oxidasa muestra una estructura de sitio activo de molibdeno diferente en comparación con el tipo silvestre. Este cambio estructural, que involucra la coordinación de la glutamina, explica las propiedades alteradas del mutante.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Estructural Biología estructural.
- Química computacional es la química computacional.
Sus antecedentes:
- La sulfito oxidasa es una enzima vital en la fisiología humana.
- Las mutaciones clínicas pueden alterar la estructura y la función de las enzimas.
- La mutación de la Arginina 160 --> Glutamina afecta la actividad de la sulfito oxidasa.
Objetivo del estudio:
- Para investigar los cambios estructurales en el sitio activo de molibdeno de la Arginina 160 --> Glutamina sulfito oxidasa mutante.
- Para entender cómo estos cambios estructurales se relacionan con las propiedades de la enzima mutante.
Principales métodos:
- Espectroscopia de absorción de rayos X (XAS) para sondear el sitio del molibdeno.
- Cálculos de la teoría funcional de la densidad (DFT) para el análisis estructural y electrónico.
Principales resultados:
- La enzima mutante exhibe un sitio activo de molibdeno pseudo-octaédrico de seis coordenadas.
- El átomo Oepsilon de la glutamina tiene las coordenadas del centro de molibdeno en el mutante.
- La enzima de tipo salvaje tiene un sitio de molibdeno piramidal de base cuadrada de cinco coordenadas.
Conclusiones:
- La diferencia de coordinación en el sitio del molibdeno explica las propiedades previamente reportadas de la Arginina 160 --> Glutamina mutante.
- Los conocimientos estructurales sobre las mutaciones enzimáticas son cruciales para comprender las funciones fisiológicas.
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