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Molecular interaction of artemisinin with translationally controlled tumor protein (TCTP) of Plasmodium falciparum

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 pro...

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Main Authors: Eichhorn, Tolga (Author) , Winter, Dominic (Author) , Büchele, Berthold (Author) , Dirdjaja, Natalie (Author) , Frank, Martin (Author) , Lehmann, Wolf-Dieter (Author) , Mertens, Rolf (Author) , Krauth-Siegel, Renate (Author) , Simmet, Thomas (Author) , Granzin, Joachim (Author) , Efferth, Thomas (Author)
Format: Article (Journal)
Language:English
Published: 2013
In: Biochemical pharmacology
Year: 2012, Volume: 85, Issue: 1, Pages: 38-45
ISSN:1873-2968
DOI:10.1016/j.bcp.2012.10.006
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.bcp.2012.10.006
Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S0006295212006788
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Author Notes:Tolga Eichhorn, Dominic Winter, Berthold Büchele, Natalie Dirdjaja, Martin Frank, Wolf-Dieter Lehmann, Rolf Mertens, R. Luise Krauth-Siegel, Thomas Simmet, Joachim Granzin, Thomas Efferth
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Summary: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.
Item Description:Available online 17 October 2012
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Physical Description:Online Resource
ISSN:1873-2968
DOI:10.1016/j.bcp.2012.10.006

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