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
Article
Dans Anglais
| 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.
Texte intégral:
Disponible
Indice:
IMSEAR (Asie du Sud-Est)
Sujet Principal:
Phénytoïne
/
Liaison aux protéines
/
Conformation des protéines
/
Sites de fixation
/
Simulation numérique
/
Humains
/
Modèles moléculaires
/
Catalyse
/
Glycoprotéine P
/
Modèles chimiques
Type d'étude:
Étude pronostique
langue:
Anglais
Texte intégral:
Indian J Biochem Biophys
Année:
2013
Type:
Article
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