English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/142176
COMPARTIR / IMPACTO:
Estadísticas
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:
Título

Plasmodium falciparum Choline Kinase Inhibition Leads to a Major Decrease in Phosphatidylethanolamine Causing Parasite Death

AutorSerrán-Aguilera, L.; Denton, H.; Rubio-Ruiz, B.; López-Gutiérrez, B.; Entrena, A.; Izquierdo, L.; Smith, T.K.; Conejo-García, A.; Hurtado-Guerrero, R.
Fecha de publicación2016
EditorNature Publishing Group
CitaciónScientific Reports 6 (2016)
ResumenMalaria is a life-threatening disease caused by different species of the protozoan parasite Plasmodium, with P. falciparum being the deadliest. Increasing parasitic resistance to existing antimalarials makes the necessity of novel avenues to treat this disease an urgent priority. The enzymes responsible for the synthesis of phosphatidylcholine and phosphatidylethanolamine are attractive drug targets to treat malaria as their selective inhibition leads to an arrest of the parasite's growth and cures malaria in a mouse model. We present here a detailed study that reveals a mode of action for two P. falciparum choline kinase inhibitors both in vitro and in vivo. The compounds present distinct binding modes to the choline/ethanolamine-binding site of P. falciparum choline kinase, reflecting different types of inhibition. Strikingly, these compounds primarily inhibit the ethanolamine kinase activity of the P. falciparum choline kinase, leading to a severe decrease in the phosphatidylethanolamine levels within P. falciparum, which explains the resulting growth phenotype and the parasites death. These studies provide an understanding of the mode of action, and act as a springboard for continued antimalarial development efforts selectively targeting P. falciparum choline kinase.
URIhttp://hdl.handle.net/10261/142176
DOI10.1038/srep33189
Identificadoresdoi: 10.1038/srep33189
issn: 2045-2322
Aparece en las colecciones: (IQFR) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
srep33189.pdf1,22 MBAdobe PDFVista previa
Visualizar/Abrir
Mostrar el registro completo
 

Artículos relacionados:


NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.