title: Identification of the Schistosoma mansoni molecular target for the antimalarial drug artemether.
abstract: 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.
authors: Department of Physics, Sapienza University of Rome, Rome, Italy.
authors: Rosalba
authors: R
authors: Lepore
authors: Silvia
authors: S
authors: Simeoni
authors: Domenico
authors: D
authors: Raimondo
authors: Antonia
authors: A
authors: Caroli
authors: Anna
authors: A
authors: Tramontano
authors: Allegra
authors: A
authors: Via
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D000077549:Artemether; D037621:Artemisinins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001665:Binding Sites; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019295:Computational Biology / Q000379:methods*; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology; D011485:Protein Binding; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012550:Schistosoma mansoni / Q000187:drug effects* / Q000201:enzymology; D012555:Schistosomiasis mansoni / Q000188:drug therapy / Q000469:parasitology; D012556:Schistosomicides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D016415:Sequence Alignment; D013045:Species Specificity; D040681:Structural Homology, Protein; D013816:Thermodynamics
chemical_list: C513500:ATP6 protein, Plasmodium falciparum; D000962:Antimalarials; D037621:Artemisinins; D012556:Schistosomicides; D000077549:Artemether; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases