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Una N-demetilasa oxidativa revela la transición de PAS desde el sensor ubicuo a la enzima
Mary Ortmayer1, Pierre Lafite1, Binuraj R K Menon1
1Manchester Institute of Biotechnology, School of Chemistry, 131 Princess Street, University of Manchester, Manchester M1 7DN, UK.
Nature
|November 17, 2016
Resumen
Los investigadores descubrieron la primera enzima con un dominio Per-ARNT-Sim (PAS), un módulo de proteína versátil. Esta nueva enzima oxida la dimetilamina, lo que demuestra el dominio PAS
Área de la Ciencia:
- La bioquímica
- Enzimología
- Biología estructural
Sus antecedentes:
- El dominio Per-ARNT-Sim (PAS) es un módulo de señalización conservado que detecta diversas señales ambientales.
- Los dominios PAS se unen a varios ligandos como el hemo y las flavinas, pero la actividad enzimática era desconocida anteriormente.
- La versatilidad estructural del andamio PAS sugiere el potencial para funciones catalíticas.
Objetivo del estudio:
- Para caracterizar el primer dominio PAS enzimático identificado.
- Para aclarar el mecanismo de una nueva N-demetilasa oxidativa dependiente de hemo.
- Para explorar el potencial catalítico del andamio PAS.
Principales métodos:
- Caracterización bioquímica de la nueva enzima.
- Análisis estructural del dominio PAS.
- Investigación de la activación del oxígeno con ayuda del sustrato.
Principales resultados:
- Identificó y caracterizó el primer dominio PAS enzimático, una N-demetilasa oxidativa dependiente de hemo.
- La enzima utiliza cofactores de hemo, mononucleótido de flavina, 2Fe-2S y ácido tetrahidrólico.
- Los datos estructurales revelan que el dominio PAS se une al hemo y al sustrato, facilitando la activación del oxígeno.
Conclusiones:
- El dominio PAS puede hacer la transición de un sensor a una enzima.
- Este hallazgo amplía las funciones conocidas del omnipresente andamio PAS.
- La adaptabilidad del andamio PAS sugiere potencial para el diseño de enzimas artificiales.
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