Combined receptor-based and ligand-based approach to delineate the mode of binding of guaianolide-endoperoxides to PfATP6.
Bioorg Med Chem Lett
; 22(17): 5410-4, 2012 Sep 01.
Article
en En
| MEDLINE
| ID: mdl-22877631
ABSTRACT
Plasmodium falciparum calcium-ATPase (PfATP6) has been reported to be a target of artemisinin and related endoperoxides. In this study, a series of previously reported guaianolide-endoperoxides (thaperoxides) were docked into a homology model of PfATP6 and also used to develop a pharmacophore model. This combined approach led to useful insights into the binding determinants of thaperoxides to the malarial enzyme. In addition, in silico mutagenesis and molecular dynamics suggested the importance of Phe264 and the electrostatic interactions between Lys260 in helix H3 and Lys1036 and Asp1038 in L6/7 loop for the binding of thaperoxides. These results could help in the design of more potent inhibitors of PfATP6.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Plasmodium falciparum
/
ATPasas Transportadoras de Calcio
/
Sesquiterpenos de Guayano
/
Antimaláricos
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Egipto