Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0024530 (
malaria
)
44,886
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Apicomplexan parasites include the causative agents of
malaria
and toxoplasmosis. Cell-based screens in
Toxoplasma
previously identified a chemical modulator of calcium signaling (
ENH1
) that blocked parasite egress from host cells and exhibited potent antiparasitic activity. To identify the targets of
ENH1
, we adapted thermal proteome profiling to
Toxoplasma
, which revealed calcium-dependent protein kinase 1 (CDPK1) as a target. We confirmed the inhibition of CDPK1 by
ENH1
in vitro and in parasites by comparing alleles sensitive or resistant to
ENH1
. CDPK1 inhibition explained the block in egress; however, the effects of
ENH1
on calcium homeostasis and parasite viability were CDPK1-independent, implicating additional targets. Thermal proteome profiling of lysates from parasites expressing the resistant allele of CDPK1 identified additional candidates associated with the mitochondria and the parasite pellicle-compartments that potentially function in calcium release and homeostasis. Our findings illustrate the promise of thermal profiling to identify druggable targets that modulate calcium signaling in apicomplexan parasites.
...
PMID:Identifying the Target of an Antiparasitic Compound in
Toxoplasma
Using Thermal Proteome Profiling. 3259 28
