Journal of chemical information and modeling · 2011
Identification of the Schistosoma mansoni molecular target for the antimalarial drug artemether.
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Lepore Rosalba, Simeoni Silvia, Raimondo Domenico, Caroli Antonia, Tramontano Anna, Via Allegra
Аннотация
Plasmodium falciparum and Schistosoma mansonii are the parasites responsible for most of the malaria and schistosomiasis cases in the world. Notwithstanding their many differences, the two agents have striking similarities in that they both are blood feeders and are targets of an overlapping set of drugs, including the well-known artemether molecule. Here we explore the possibility of using the known information about the mode of action of artemether in Plasmodium to identify the molecular target of the drug in Schistosoma and provide evidence that artemether binds to SmSERCA, a putative Ca²⁺-ATPase of Schistosoma . We also predict the putative binding mode of the molecule for both its Plasmodium and Schistosoma targets. Our analysis of the mode of binding of artemether to Ca²⁺-ATPases also provides an explanation for the apparent paradox that, although the molecule has no side effect in humans, it has been shown to possess antitumoral activity.
Предметные рубрики MeSH
Amino Acid SequenceAnimalsAntimalarialsArtemetherArtemisininsBinding SitesCalcium-Transporting ATPasesComputational BiologyHumansMalaria, FalciparumModels, MolecularMolecular Sequence DataOxidation-ReductionPlasmodium falciparumProtein BindingSarcoplasmic Reticulum Calcium-Transporting ATPasesSchistosoma mansoniSchistosomiasis mansoniSchistosomicidesSequence AlignmentSpecies SpecificityStructural Homology, ProteinThermodynamics