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Sirt5 es una proteína lysine demalonylase y desuccinylase dependiente de NAD
Jintang Du1, Yeyun Zhou, Xiaoyang Su
1Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.
Science (New York, N.Y.)
|November 15, 2011
Resumen
Sirt5, una sirtuina de mamíferos, elimina de manera eficiente los grupos succinilo y malonilo de las proteínas. Esta reversión de la modificación de la proteína lisina por Sirt5 sugiere un nuevo mecanismo regulador in vivo.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Molecular Biología Molecular
- Modificaciones después de la traducción.
Sus antecedentes:
- Las sirtuinas (proteínas reguladoras de la información silenciosa 2) son enzimas dependientes del NAD+ que participan en procesos biológicos cruciales.
- Los mamíferos poseen siete sirtuinas (Sirt1-Sirt7), con Sirt4-Sirt7 exhibiendo actividad limitada o nula de la desacetilasa.
Objetivo del estudio:
- Para investigar la actividad enzimática de Sirt5 más allá de la desacetilación.
- Identificar y caracterizar el papel de Sirt5 en la succinilación y malonilación de la proteína lisina.
Principales métodos:
- Ensayos enzimáticos in vitro para determinar la actividad de desuccinilase y demalonilase de Sirt5.
- Espectrometría de masas para identificar las proteínas succiniladas y maloniladas en mamíferos.
- Análisis de ratones knockout Sirt5 para evaluar los efectos in vivo en la succinilación de proteínas.
Principales resultados:
- Sirt5 demostró una eficiente actividad in vitro de la proteína lisina desuccinylase y la demalonilase.
- Se identificaron residuos específicos (Arg105, Tyr102) en la bolsa de acilo de Sirt5 como clave para la preferencia del sustrato.
- Se observó un aumento de la succinilación de la carbamoilfosfato sintasa 1 en ratones con deficiencia de Sirt5.
Conclusiones:
- Sirt5 funciona como una desuccinylase y demalonylase primaria, revirtiendo las modificaciones específicas posteriores a la traducción.
- La succinilación de la proteína lisina es una modificación reversible regulada por Sirt5 in vivo.
- Sirt5 juega un papel importante en la regulación de las vías metabólicas a través de la desucinilación.
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