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¿Existe un intermediario Ni-metilo en el mecanismo de la metil-coenzima M reductasa?
Shi-lu Chen1, Vladimir Pelmenschikov, Margareta R A Blomberg
1Department of Physics, Stockholm University, SE-10691 Stockholm, Sweden. shlchen@physto.se
Journal of the American Chemical Society
|July 3, 2009
Resumen
La formación de metil-Ni ((F ((430)) en la metil-coenzima M reductasa (MCR) depende de la acidez del sustrato. Los haluros de metilo facilitan esto, pero el sustrato nativo es energéticamente inaccesible, alineándose con los hallazgos experimentales.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Química computacional es la química computacional.
- Enzimología Enzimología.
Sus antecedentes:
- La metil-coenzima M reductasa (MCR) es crucial para la metanogénesis.
- Comprender el sitio activo, en particular la formación de metil-Ni (F430), es clave para la función de la MCR.
- Estudios previos han explorado los mecanismos de MCR con varios sustratos.
Objetivo del estudio:
- Investigar las vías de formación de las especies de metil-Ni (F430) en MCR.
- Para determinar la influencia de la acidez del grupo saliente del sustrato en la formación de metil-Ni(F(430)).
- Para comparar la viabilidad energética de la formación de metil-Ni (F430) con diferentes sustratos, incluido el nativo.
Principales métodos:
- Utilizó el método funcional de densidad híbrida B3LYP para cálculos teóricos.
- Se empleó un modelo de sitio activo derivado de las estructuras cristalinas de rayos X de MCR.
- Reacciones simuladas con yoduro de metilo, bromuro de metilo, cloruro de metilo y sulfuro de dimetilo como sustratos.
Principales resultados:
- Los cálculos revelaron que la formación de metil-Ni(F(430)) está significativamente influenciada por la acidez del grupo saliente del sustrato.
- Las especies de metil-Ni (((F ((430)) se observaron computacionalmente con sustratos de haluro de metilo.
- El análisis energético indicó que la formación de metil-Ni (((F ((430)) a partir del sustrato nativo (metil-coenzima M) es energéticamente desfavorable.
Conclusiones:
- La acidez del grupo saliente es un factor crítico que rige la formación de metil-Ni (((F ((430)) en MCR.
- Los haluros de metilo son más conducentes a la formación de las especies de metil-Ni (F430) que el sustrato nativo.
- Los hallazgos computacionales son consistentes con las observaciones experimentales existentes con respecto a la actividad de MCR.
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