Open AccessPREDICTED BINDING MODE OF ANDROGRAPHOLIDE AND ITS DERIVATIVES BOUND TO PLASMODIUM FALCIPARUM GERANYLGERANYL PYROPHOSPHATE SYNTHASE
Author(s) -
Andrianopsyah Mas Jaya Putra,
Chaidir Chaidir,
Muhammad Hanafi,
Arry Yanuar
Publication year - 2017
Publication title -
international journal of applied pharmaceutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.238
H-Index - 15
ISSN - 0975-7058
DOI - 10.22159/ijap.2017.v9s1.54_60
Subject(s) - andrographolide , andrographis paniculata , plasmodium falciparum , stereochemistry , chemistry , docking (animal) , active site , atp synthase , geranylgeranyl pyrophosphate , biochemistry , biology , enzyme , malaria , medicine , prenylation , alternative medicine , nursing , pathology , immunology
Objective: Andrographolide is a major secondary metabolite in the Indonesian herb sambiloto (Andrographis paniculata). It displays a moderateantiplasmodial activity against the chloroquine-resistant strain of Plasmodium falciparum. This study aimed to investigate andrographolide inhibitionof geranylgeranyl pyrophosphate synthase (GGPPS) by andrographolide molecular docking.Methods: A comparative modeling of P. falciparum GGPPS was conducted using one of the Plasmodium vivax GGPPS crystal structures as a template.The best model from this comparative modeling was then used in a molecular docking to investigate the binding mode of andrographolide in theP. falciparum GGPPS active site.Results: In the P. falciparum GGPPS active site, andrographolide is situated with its double rings pointing toward the hydrophobic pocket, while itslactone group is positioned between first aspartate-rich motif and second aspartate-rich motif of the catalytic pocket.Conclusions: In the active site, andrographolide is situated with its double rings pointing toward the hydrophobic pocket, while its lactone group ispositioned in the catalytic pocket.