UV-triggered Affinity Capture Identifies Interactions between the Plasmodium falciparum Multidrug Resistance Protein 1 (PfMDR1) and Antimalarial Agents in Live Parasitized Cells
Autor: | Ralf Brunner, David A. Fidock, Christoph Boss, Caroline L. Ng, Reto Brun, Ingrid B. Müller, Paul S. Callaghan, Bibia Heidmann, Till S. Voss, Sergio Wittlin, Romain Siegrist, I. J. Frame, Olivier Corminboeuf, Myles H. Akabas, Amélie Le Bihan, Richard W. D. Welford, Michelle F. Paguio, Corinna Mattheis, Paul D. Roepe, Hamed Aissaoui, Paul Jenö, Suzette Moes, Christoph Binkert |
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Rok vydání: | 2013 |
Předmět: |
Photoaffinity labeling
Ultraviolet Rays Plasmodium falciparum Molecular Bases of Disease Cell Biology Drug action Biology biology.organism_classification Biochemistry Plasmodium Virology Antimalarials Multidrug Resistance Protein 1 biology.protein Animals ATP Binding Cassette Transporter Subfamily B Member 1 Antimalarial Agent Mode of action Molecular Biology P-glycoprotein |
Zdroj: | Journal of Biological Chemistry. 288:22576-22583 |
ISSN: | 0021-9258 |
Popis: | A representative of a new class of potent antimalarials with an unknown mode of action was recently described. To identify the molecular target of this class of antimalarials, we employed a photo-reactive affinity capture method to find parasite proteins specifically interacting with the capture compound in living parasitized cells. The capture reagent retained the antimalarial properties of the parent molecule (ACT-213615) and accumulated within parasites. We identified several proteins interacting with the capture compound and established a functional interaction between ACT-213615 and PfMDR1. We surmise that PfMDR1 may play a role in the antimalarial activity of the piperazine-containing compound ACT-213615. |
Databáze: | OpenAIRE |
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