The anthraquinone emodin inhibits the non-exported FIKK kinase from Plasmodium falciparum |
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| Affiliation: | 1. Internal Medicine Residency, Boonshoft School of Medicine at WSU;2. Wright-Patterson Medical Center, Wright-Patterson Air Force Base;1. DeWitt-Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL;2. Division of Plastic and Reconstructive Surgery, Department of Pediatric Surgery, Miami Children’s Hospital, Miami, FL;3. Department of Pathology, Miami Children’s Hospital, Miami, FL;4. Division of Surgical Oncology, Department of Surgery, Herbert Wertheim College of Medicine, Florida International University, Miami, FL;5. Department of Pediatric Surgery, Miami Children’s Hospital, Miami, FL |
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| Abstract: | The FIKK family of kinases is unique to parasites of the Apicomplexan order, which includes all malaria parasites. Plasmodium falciparum, the most virulent form of human malaria, has a family of 19 FIKK kinases, most of which are exported into the host red blood cell during malaria infection. Here, we confirm that FIKK 8 is a non-exported member of the FIKK kinase family. Through expression and purification of the recombinant kinase domain, we establish that emodin is a relatively high-affinity (IC50 = 2 μM) inhibitor of PfFk8. Closely related anthraquinones do not inhibit PfFk8, suggesting that the particular substitution pattern of emodin is critical to the inhibitory pharmacophore. This first report of a P. falciparum FIKK kinase inhibitor lays the groundwork for developing specific inhibitors of the various members of the FIKK kinase family in order to probe their physiological function. |
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| Keywords: | Malaria Kinase FIKK kinase Secreted Emodin Anthraquinone Fk" },{" #name" :" keyword" ," $" :{" id" :" k0045" }," $$" :[{" #name" :" text" ," _" :" FIKK [PheIleIleLyscontaining] kinase PfFk8" },{" #name" :" keyword" ," $" :{" id" :" k0055" }," $$" :[{" #name" :" text" ," $$" :[{" #name" :" italic" ," _" :" Plasmodium falciparum" },{" #name" :" __text__" ," _" :" FIKK kinase 8 H3" },{" #name" :" keyword" ," $" :{" id" :" k0065" }," $$" :[{" #name" :" text" ," _" :" histone 3 H4" },{" #name" :" keyword" ," $" :{" id" :" k0075" }," $$" :[{" #name" :" text" ," _" :" histone 4 IFA" },{" #name" :" keyword" ," $" :{" id" :" k0085" }," $$" :[{" #name" :" text" ," _" :" indirect immunofluorescence assay DABCO" },{" #name" :" keyword" ," $" :{" id" :" k0095" }," $$" :[{" #name" :" text" ," _" :" 1,4-diazabicyclo[2.2.2]octane DAPI" },{" #name" :" keyword" ," $" :{" id" :" k0105" }," $$" :[{" #name" :" text" ," _" :" 4′,6-diamidino-2-phenylindole |
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