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Bases estructurales para el reconocimiento molecular del ácido fólico por los receptores de folato

Chen Chen¹, Jiyuan Ke, X Edward Zhou

¹Program for Structural Biology and Drug Discovery, Van Andel Research Institute, 333 Bostwick Avenue North East, Grand Rapids, Michigan 49503, USA.

|July 16, 2013

Resumen

Los investigadores determinaron la estructura cristalina del receptor de folato alfa (FRα) unido al ácido fólico. Esta estructura revela cómo FRα se une al folato, ofreciendo una plantilla para el desarrollo de terapias dirigidas contra el cáncer.

Área de la Ciencia:

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

Sus antecedentes:

Los receptores de folato (FRα, FRβ, FRγ) son glicoproteínas de la superficie celular que son cruciales para la absorción del folato.
La expresión elevada de FRα en muchos tipos de cáncer impulsa el crecimiento tumoral, por lo que es un objetivo terapéutico.

Objetivo del estudio:

Para dilucidar la base estructural de la unión del folato al receptor alfa del folato (FRα).
Proporcionar una plantilla estructural para el diseño de nuevos fármacos contra el cáncer dirigidos a FRα.

Principales métodos:

Determinó la estructura cristalina del FRα humano en complejo con ácido fólico a una resolución de 2,8 Å.

Principales resultados:

FRα posee una estructura globular con ocho enlaces disulfuro y una bolsa profunda y conservada de unión al folato.
El grupo pteroato del ácido fólico está enterrado, mientras que el grupo glutamato está expuesto, lo que permite la conjugación de fármacos.
Las extensas interacciones receptor-ligando explican la alta afinidad de unión al folato.

Conclusiones:

La estructura determinada del ácido FRα-fólico proporciona una visión crítica de la unión del folato.
Esta información estructural puede guiar el desarrollo de terapias más específicas y efectivas dirigidas a los receptores de folato.

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