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Bases estructurales para la transferencia de metilo por una enzima SAM radical.
Amie K Boal1, Tyler L Grove, Monica I McLaughlin
1Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA.
Science (New York, N.Y.)
|April 30, 2011
Resumen
Las enzimas radicales S-adenosil-L-metionina (SAM) RlmN y Cfr metilanan el ARN ribosomal 23S. Los estudios estructurales revelan que RlmN utiliza una sola molécula SAM y un sitio activo para realizar su compleja reacción de metilación.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Molecular Biología Molecular
- Biología Estructural Biología estructural.
Sus antecedentes:
- Las enzimas radicales S-adenosil-L-metionina (SAM) RlmN y Cfr son cruciales para la metilación del ARN ribosomal 23S.
- Esta metilación ocurre en la posición C2 o C8 de la adenosina 2503, afectando la función del ribosoma.
Objetivo del estudio:
- Para aclarar los mecanismos estructurales por los cuales RlmN utiliza S-adenosil-L-metionina (SAM) para la metilación del ARN ribosomal.
- Para entender cómo RlmN logra su complejo proceso de metilación en dos pasos dentro de un solo sitio activo.
Principales métodos:
- Se empleó cristalografía de rayos X para determinar las estructuras de RlmN y su complejo con SAM.
- El análisis estructural se centró en la coordinación del grupo [4Fe-4S] y el posicionamiento de los residuos clave y SAM.
Principales resultados:
- Las estructuras cristalinas revelaron que una sola molécula SAM coordina el cúmulo [4Fe-4S] en RlmN.
- El residuo Cys355 conservado es S-metilado y posicionado cerca del grupo metilo SAM, lo que indica un sitio de unión compartido para ambas etapas de metilación.
- Esto sugiere que RlmN emplea economía estructural al utilizar un sitio para ambas reacciones dependientes de SAM.
Conclusiones:
- RlmN cataliza eficientemente la metilación en dos pasos del ARN ribosomal 23S mediante la utilización de un único sitio activo para la unión SAM y la transferencia de metilo.
- La enzima aprovecha las distintas reactividades de SAM dentro de un bolsillo de unión estructuralmente conservado, mostrando un elegante mecanismo bioquímico.
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