In silico exploration of phenytoin binding site in two catalytic states of human P-glycoprotein models.
Indian J Biochem Biophys
;
2013 Feb; 50(1): 7-13
Artículo
en Inglés
| IMSEAR
| ID: sea-147280
ABSTRACT
P-glycoprotein (P-gp), an ATP-dependant efflux pump transports a wide range of substrates across cellular membranes. Earlier studies have identified drug efflux due to the over-expression of P-gp as one of the causes for the resistance of phenytoin, an anti-epileptic drug (AED). While no clear evidence exists on the specific characteristics of phenytoin association with the human P-gp, this study employed structure-based computational approaches to identify its binding site and the underlying interactions. The identified site was validated with that of rhodamine, a widely accepted reference and an experimental probe. Further, an in silico proof-of-concept for phenytoin interactions and its decreased binding affinity with the closed-state of human P-gp model was provided in comparison with other AEDs. This is the first report to provide insights into the phenytoin binding site and possibly better explain its efflux by P-gp.
Texto completo:
Disponible
Índice:
IMSEAR (Asia Sudoriental)
Asunto principal:
Fenitoína
/
Unión Proteica
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Conformación Proteica
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Sitios de Unión
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Simulación por Computador
/
Humanos
/
Modelos Moleculares
/
Catálisis
/
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP
/
Modelos Químicos
Tipo de estudio:
Estudio pronóstico
Idioma:
Inglés
Revista:
Indian J Biochem Biophys
Año:
2013
Tipo del documento:
Artículo
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