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Las estructuras cristalinas del sensor de adenilato de la proteína quinasa activada por AMP de la levadura de fisión
Robert Townley1, Lawrence Shapiro
1Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
Science (New York, N.Y.)
|February 10, 2007
Resumen
La proteína quinasa activada por monofosfato de adenosina (AMPK) regula la energía celular. Las estructuras cristalinas revelan que el trifosfato de adenosina (ATP) y el monofosfato de adenosina (AMP) se unen de manera competitiva, lo que influye en la actividad enzimática y el equilibrio energético.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Estructural Biología estructural.
- Biología Molecular Biología Molecular
Sus antecedentes:
- La proteína quinasa activada por monofosfato de adenosina (AMPK) es un regulador crucial de la homeostasis de la energía celular.
- La actividad de la AMPK está modulada por las concentraciones intracelulares de trifosfato de adenosina (ATP) y monofosfato de adenosina (AMP).
Objetivo del estudio:
- Para aclarar la base estructural de la unión de adenilato en AMPK.
- Para entender cómo la unión de ATP y AMP regula la función de AMPK.
Principales métodos:
- Se empleó cristalografía de rayos X para determinar las estructuras del dominio de unión al adenilato alfabetagamma del AMPK.
- Las estructuras se resolvieron en 2.9 y 2.6 A para los estados ligados a ATP y AMP, respectivamente.
Principales resultados:
- El ATP y el AMP se unen competitivamente a un sitio compartido dentro de la subunidad gamma.
- La unión de ATP y AMP influye en los residuos cerca de las mutaciones que afectan la función.
- El ATP se une sin contraiones, mejorando las interacciones electrostáticas en una región reguladora clave.
Conclusiones:
- La unión competitiva de ATP y AMP en un solo sitio proporciona un mecanismo para la detección de energía de AMPK.
- Las ideas estructurales revelan cómo la unión de ATP afecta conformacionalmente a la enzima, afectando su región reguladora.
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