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Estructura cristalina del dominio catalítico de la fosfatasa controladora del ciclo celular humano, Cdc25A

E B Fauman¹, J P Cogswell, B Lovejoy

¹Department of Biological Chemistry, The University of Michigan, Ann Arbor 48109-1055, USA. fauman@umich.edu

|May 30, 1998

Resumen

La estructura de la fosfatasa humana Cdc25A revela un nuevo pliegue, distinto de otras fosfatasas pero similar a las proteínas de transferencia de azufre. Este hallazgo ofrece información sobre la regulación del ciclo celular y los posibles mecanismos de autoinhibición.

Área de la Ciencia:

La bioquímica es la bioquímica.
Biología Estructural Biología estructural.
Biología celular Biología celular.

Sus antecedentes:

Las fosfatasas Cdc25 son reguladores cruciales de las quinasas de división celular.
Comprender su estructura es clave para descifrar el control del ciclo celular.

Objetivo del estudio:

Para determinar la estructura 3D del dominio catalítico Cdc25A del cuerpo humano.
Para aclarar la base estructural de la actividad y regulación enzimática de Cdc25A.

Principales métodos:

Cristalografía de rayos X con una resolución de 2.3 A.
Alineaciones de secuencias basadas en la estructura. alineamientos de secuencias basados en la estructura.

Principales resultados:

El dominio catalítico Cdc25A humano posee un pliegue alfa/beta único, similar al de la rodanesa, no visto previamente en las fosfatasas.
Un enlace disulfuro entre Cys-430 y Cys-384 sugiere un potencial mecanismo de autoinhibición inducido por el estrés oxidativo.
Asp-383 juega un papel estructural, no actúa como un ácido general; Glu-431 se propone como el ácido general.

Conclusiones:

La estructura Cdc25A revela un nuevo pliegue con implicaciones para la clasificación de la fosfatasa.
Los hallazgos sugieren un mecanismo regulador que involucra estrés oxidativo e identifican una potencial homología estructural con las MAP quinasa fosfatasas y ACR2.

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