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Capturando la estructura de un intermediario catalítico de ARN: la ribozima cabeza de martillo

W G Scott¹, J B Murray, J R Arnold

¹MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, England.

Science (New York, N.Y.)

|December 20, 1996

Resumen

Se resolvió la estructura cristalina de la ribozima cabeza de martillo, revelando su pliegue activo. Los iones metálicos divalentes inducen cambios conformacionales en el sitio activo, lo que facilita la autoescisión.

Área de la Ciencia:

La bioquímica es la bioquímica.
Biología Estructural Biología estructural.
La catálisis del ARN por ARN.

Sus antecedentes:

Las ribozimas de cabeza de martillo son enzimas de ARN cruciales capaces de auto-clivado.
Comprender su relación estructura-función es clave para la biología del ARN.

Objetivo del estudio:

Para determinar la estructura cristalina de una ribozima cabeza de martillo no modificada.
Para investigar los cambios conformacionales inducidos por los iones metálicos divalentes durante la catálisis.

Principales métodos:

Se utilizó la cristalografía de rayos X para resolver la estructura de la ribozima cabeza de martillo.
La criotrapado a pH activo capturó un intermediario catalítico.

Principales resultados:

Se aclaró el pliegue biológicamente activo de la ribozima no modificada.
Se demostró que los cationes divalentes se unen al fosfato en el sitio de la escisión, formando un intermediario conformacional.
Los cambios conformacionales se localizan en el sitio activo, acercándose al estado de transición.

Conclusiones:

La ribozima cabeza de martillo adopta un pliegue conservado a través de diferentes modificaciones.
La unión de iones metálicos y los cambios conformacionales subsiguientes son críticos para la catálisis de la ribozima cabeza de martillo.

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