Gene expression signatures and small-molecule compounds link a protein kinase to Plasmodium falciparum motility.
Nat Chem Biol
; 4(6): 347-56, 2008 Jun.
Article
em En
| MEDLINE
| ID: mdl-18454143
ABSTRACT
Calcium-dependent protein kinases play a crucial role in intracellular calcium signaling in plants, some algae and protozoa. In Plasmodium falciparum, calcium-dependent protein kinase 1 (PfCDPK1) is expressed during schizogony in the erythrocytic stage as well as in the sporozoite stage. It is coexpressed with genes that encode the parasite motor complex, a cellular component required for parasite invasion of host cells, parasite motility and potentially cytokinesis. A targeted gene-disruption approach demonstrated that pfcdpk1 seems to be essential for parasite viability. An in vitro biochemical screen using recombinant PfCDPK1 against a library of 20,000 compounds resulted in the identification of a series of structurally related 2,6,9-trisubstituted purines. Compound treatment caused sudden developmental arrest at the late schizont stage in P. falciparum and a large reduction in intracellular parasites in Toxoplasma gondii, which suggests a possible role for PfCDPK1 in regulation of parasite motility during egress and invasion.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Plasmodium falciparum
/
Proteínas Quinases
/
Adenina
/
Regulação Enzimológica da Expressão Gênica
/
Proteínas de Protozoários
/
Cicloexilaminas
/
Malária
/
Antimaláricos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Nat Chem Biol
Assunto da revista:
BIOLOGIA
/
QUIMICA
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos