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La unión alostérica de nucleósidos trifosfatos a la ARN polimerasa regula el alargamiento de la transcripción
J E Foster1, S F Holmes, D A Erie
1Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599, USA.
Cell
|August 21, 2001
Resumen
Los investigadores descubrieron un nuevo sitio de unión alostérico en la E. coli ARN polimerasa. La unión de nucleótidos templados a este sitio activa la enzima, aumentando la tasa de alargamiento de la transcripción.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- La bioquímica es la bioquímica.
- La cinética de las enzimas.
Sus antecedentes:
- La regulación de la transcripción involucra estados conformacionales de la ARN polimerasa.
- Los factores que controlan estos estados no se comprenden completamente.
- Comprender la dinámica de la ARN polimerasa es crucial para el control de la expresión génica.
Objetivo del estudio:
- Para investigar los factores que controlan los estados conformacionales de la ARN polimerasa.
- Para aclarar el mecanismo de regulación de la incorporación de nucleótidos.
- Para identificar la regulación alostérica en la función de la ARN polimerasa.
Principales métodos:
- Cinética del estado transitorio para estudiar la incorporación de un solo nucleótido.
- Análisis de la cinética enzimática de la ARN polimerasa de E. coli.
- Caracterización de los sitios de unión de nucleótidos.
Principales resultados:
- La ARN polimerasa de E. coli posee un sitio de unión alostérico distinto del sitio catalítico.
- La unión de trifosfatos nucleósidos templados (NTP) al sitio alostérico aumenta las tasas de incorporación de nucleótidos.
- Las NTP no templadas no se unen ni afectan el sitio alostérico.
- La ARN polimerasa existe en estados catalíticos lentos (no activados) y rápidos (activados).
- La unión de NTPs plantilladas al sitio alostérico induce la transición del estado no activado al estado activado.
Conclusiones:
- Un sitio alostérico en la polimerasa de ARN de E. coli regula la elongación de la transcripción.
- La unión de NTP con plantilla a este sitio activa la enzima para una incorporación más rápida de nucleótidos.
- Este mecanismo proporciona información sobre el control de la dinámica conformacional de la ARN polimerasa durante la transcripción.
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