Polymyxin B inhibits the chaperone activity of Plasmodium falciparum Hsp70

• DOI: 10.1007/s12192-017-0797-6
• Publication Date: 2017-04-28T20:07:51Z
• Authors: Tawanda Zininga; Ofentse J. Pooe; Pertunia B. Makhado; Lebogang Ramatsui; Earl Prinsloo; Ikechukwu Achilonu; Heinrich Dirr; Addmore Shonhai
• Keywords: Chaperone (clinical); Polymyxin; Polymyxin B

Heat shock protein 70 (Hsp70) is a molecular chaperone that plays an important role in cellular proteostasis. Hsp70s are also implicated the survival and pathogenicity of malaria parasites. The main agent malaria, Plasmodium falciparum, expresses six Hsp70s. Of these, two (PfHsp70-1 PfHsp70-z) localize to parasite cytosol. Previously conducted gene knockout studies suggested PfHsp70-z essential, it has been demonstrated small-molecule inhibitors targeting PfHsp70-1 cause death. For this reason, both potential antimalarial targets. Two cyclic lipopeptides, colistin polymyxin B (PMB), have shown bind another heat protein, Hsp90, inhibiting its function. In current study, we investigated effect PMB on structure–function features PfHsp70-z. Using surface plasmon resonance analysis, observed directly interacts with addition, using circular dichroism spectrometric analysis combined tryptophan fluorescence measurements, modulated secondary tertiary structures Hsp70. Furthermore, inhibited basal ATPase activity function Our findings suggest associates Hsp70 inhibit light central proteostasis essential development parasites particular, our expand library target medically class chaperones.