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Published on: July 25, 2013
Estudio computacional de la isomerasa cetosteroide: conocimientos de la simulación de dinámica molecular del sustrato
Devleena Mazumder1, Kalju Kahn, Thomas C Bruice
1Department of Chemistry and Biochemistry, University of California-Santa Barbara, Santa Barbara, CA 93106, USA.
Journal of the American Chemical Society
|June 19, 2003
Resumen
Las simulaciones de dinámica molecular apoyan un mecanismo cooperativo de enlace de hidrógeno para la Delta(5)-3-Ketosteroid Isomerase (KSI). Esta enzima es la enzima
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Enzimología Enzimología.
- Biología computacional Biología computacional.
Sus antecedentes:
- La delta 5-3-cetosteroide isomerasa (KSI) cataliza la isomerización de esteroides cerca del límite de difusión.
- El mecanismo catalítico de la enzima, particularmente el papel de la catálisis ácido-base general, sigue siendo objeto de debate.
- Los mecanismos propuestos incluyen un diad catalítico o un sistema cooperativo de enlaces de hidrógeno.
Objetivo del estudio:
- Para investigar el mecanismo catalítico de la delta 5-3-cetosteroide isomerasa (KSI).
- Para diferenciar entre los mecanismos catalíticos propuestos utilizando simulaciones de dinámica molecular.
Principales métodos:
- Se realizaron simulaciones de dinámica molecular (DM) de 1,5 nanosegundos.
- Las simulaciones incluyeron estados de sustrato ligado a la enzima (E.S) y de intermedio ligado a la enzima (E.In).
- El sistema fue solvado en una caja de agua TIP3P.
Principales resultados:
- Las simulaciones de MD apoyan fuertemente un mecanismo cooperativo de enlace de hidrógeno.
- Los principales residuos Tyr14 y Asp99 forman enlaces de hidrógeno con el sustrato/intermedio.
- La dinámica del agua en el sitio activo cambia, con el agua excluida del complejo E.In debido al movimiento hidrofóbico de los residuos.
Conclusiones:
- El estudio proporciona pruebas sólidas de un mecanismo cooperativo de enlace de hidrógeno en KSI.
- Los cambios dinámicos en el sitio activo, incluida la exclusión de agua, son cruciales para la catálisis.
- Las simulaciones computacionales ofrecen información valiosa sobre los mecanismos de las enzimas.
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