Solution structure of PcFK1, a spider peptide active against Plasmodium falciparum.
Psalmopeotoxin I (PcFK1) is a 33-amino-acid residue peptide isolated from the venom of the tarantula Psalmopoeus cambridgei. It has been recently shown to possess strong antiplasmodial activity against the intra-erythrocyte stage of Plasmodium falciparum in vitro. Although the molecular target for PcFK1 is not yet determined, this peptide does not lyse erythrocytes, is not cytotoxic to nucleated mammalian cells, and does not inhibit neuromuscular function. We investigated the structural properties of PcFK1 to help understand the unique mechanism of action of this peptide and to enhance its utility as a lead compound for rational development of new antimalarial drugs. In this paper, we have determined the three-dimensional solution structure by (1)H two-dimensional NMR means of recombinant PcFK1, which is shown to belong to the ICK structural superfamily with structural determinants common to several neurotoxins acting as ion channels effectors.
Pimentel
Cyril
C
AFMB, CNRS UMR 6098 and Universités d'Aix-Marseille I and II, 31 Chemin Joseph Aiguier, 13402 Marseille Cedex 20, France.
Choi
Soo-Jin
SJ
Chagot
Benjamin
B
Guette
Catherine
C
Camadro
Jean-Michel
JM
Darbon
Hervé
H
D000818:Animals; D000962:Antimalarials / Q000737:chemistry*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry; D010963:Plasmodium falciparum / Q000187:drug effects; D012996:Solutions; D013111:Spider Venoms / Q000737:chemistry*
D000962:Antimalarials; D010455:Peptides; D012996:Solutions; D013111:Spider Venoms; C490709:psalmopeotoxin I, Psalmopoeus cambridgei