title: Molecular interaction of artemisinin with translationally controlled tumor protein (TCTP) of Plasmodium falciparum.
abstract: Malaria causes millions of death cases per year. Since Plasmodium falciparum rapidly develops drug resistance, it is of high importance to investigate potential drug targets which may lead to novel rational therapy approaches. Here we report on the interaction of translationally controlled tumor protein of P. falciparum (PfTCTP) with the anti-malarial drug artemisinin. Furthermore, we investigated the crystal structure of PfTCTP. Using mass spectrometry, bioinformatic approaches and surface plasmon resonance spectroscopy, we identified novel binding sites of artemisinin which are in direct neighborhood to amino acids 19-46, 108-134 and 140-163. The regions covered by these residues are known to be functionally important for TCTP function. We conclude that interaction of artemisinin with TCTP may be at least in part explain the antimalarial activity of artemisinin.
authors.affiliation: Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Tolga
authors.initials: T
authors.lastname: Eichhorn
authors.forename: Dominic
authors.initials: D
authors.lastname: Winter
authors.forename: Berthold
authors.initials: B
authors.lastname: Büchele
authors.forename: Natalie
authors.initials: N
authors.lastname: Dirdjaja
authors.forename: Martin
authors.initials: M
authors.lastname: Frank
authors.forename: Wolf-Dieter
authors.initials: WD
authors.lastname: Lehmann
authors.forename: Rolf
authors.initials: R
authors.lastname: Mertens
authors.forename: R Luise
authors.initials: RL
authors.lastname: Krauth-Siegel
authors.forename: Thomas
authors.initials: T
authors.lastname: Simmet
authors.forename: Joachim
authors.initials: J
authors.lastname: Granzin
authors.forename: Thomas
authors.initials: T
authors.lastname: Efferth
mesh_terms: D000962:Antimalarials / Q000737:chemistry*; D037621:Artemisinins / Q000737:chemistry*; D001665:Binding Sites; D014408:Biomarkers, Tumor / Q000737:chemistry* / Q000378:metabolism; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000378:metabolism*; D011485:Protein Binding; D015800:Protozoan Proteins / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D020349:Surface Plasmon Resonance; D000090324:Tumor Protein, Translationally-Controlled 1
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D014408:Biomarkers, Tumor; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C000715647:TPT1 protein, human; D000090324:Tumor Protein, Translationally-Controlled 1; C031327:artemisinin