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Allostery en la enfermedad y en el descubrimiento de fármacos
Ruth Nussinov1, Chung-Jung Tsai
1National Cancer Institute, Center for Cancer Research Nanobiology Program, Frederick National Laboratory for Cancer Research, SAIC-Frederick, Inc., National Cancer Institute, Frederick, MD 21702, USA. nussinor@helix.nih.gov
Cell
|April 16, 2013
Resumen
Allostery, la regulación de la función de las proteínas a través de cambios conformacionales, impacta los procesos celulares y las enfermedades. Comprender las acciones alostéricas aberrantes ofrece potencial para el desarrollo de fármacos alostéricos innovadores.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Molecular Biología Molecular
- Farmacología Farmacología.
Sus antecedentes:
- Allostery tradicionalmente describe los cambios conformacionales y funcionales dentro de las proteínas individuales.
- El concepto de alostería se extiende a las funciones celulares y los estados de enfermedad influenciados por los cambios conformacionales de las proteínas.
Objetivo del estudio:
- Aclarar el concepto de alosteria y su control sobre las actividades fisiológicas.
- Explorar cómo los mecanismos alostéricos contribuyen a la causalidad de la enfermedad.
- Para resaltar el potencial terapéutico de dirigirse a las vías alostéricas para el desarrollo de fármacos innovadores.
Principales métodos:
- Aclaración conceptual de la regulación alostérica.
- Análisis del vínculo entre los síntomas de la enfermedad celular y la desregulación alosterica molecular.
- Revisión de las estrategias de desarrollo de fármacos alostéricos.
Principales resultados:
- Los mecanismos alostéricos son reguladores cruciales de las actividades fisiológicas.
- Las acciones alostéricas aberrantes a nivel molecular están vinculadas a los síntomas de la enfermedad celular.
- La modulación alostérica presenta una vía prometedora para nuevas intervenciones terapéuticas.
Conclusiones:
- Una comprensión más profunda de la alostería es esencial para comprender los mecanismos de la enfermedad.
- Dirigirse a las vías alostéricas ofrece un potencial significativo para el desarrollo de terapias innovadoras.
- Cerrar la brecha entre los eventos alostéricos moleculares y la patología celular es clave para el futuro descubrimiento de fármacos.
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