15-Deoxyspergualin modulates Plasmodium falciparum heat shock protein function

Biochem Biophys Res Commun. 2006 Sep 22;348(2):585-92. doi: 10.1016/j.bbrc.2006.07.082. Epub 2006 Jul 28.


Heat shock proteins are essential for the survival of all cells. The C-terminal EEVD motif of Hsp70 has previously been implicated in binding 15-deoxyspergualin (DSG), an immunosuppressant with antimalarial activity whose mechanism of action is uncertain. We report the cloning, overexpression, and characterization of three members of the heat shock family, PfHsp70-1 (an Hsp70 protein with a C-terminal EEVD motif), PfHsp70-2 (an Hsp70 protein without the EEVD motif), and PfHsp70 interacting protein. The chaperone activity of PfHsp70-1, and PfHsp70-2 was enhanced by ATP and by PfHip. Interestingly, while binding of protein substrates to PfHsp70-1, PfHsp70-2 and PfHip was unaffected in the presence of DSG, the ATP enhanced chaperone activity of PfHsp70-1 but not PfHsp70-2 was stimulated further by DSG. Our finding suggests that the binding partner of DSG in the parasite cellular milieu is PfHsp70-1 and paves the way for the elucidation of the mechanism of antimalarial action of DSG.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / pharmacology
  • Animals
  • Chromatography, Affinity
  • Cloning, Molecular
  • Guanidines / pharmacology*
  • HSP70 Heat-Shock Proteins / metabolism*
  • Light
  • Molecular Chaperones / drug effects
  • Molecular Chaperones / physiology
  • Plasmodium falciparum / drug effects*
  • Scattering, Radiation


  • Guanidines
  • HSP70 Heat-Shock Proteins
  • Molecular Chaperones
  • Adenosine Triphosphate
  • gusperimus