2kfe | pdb_00002kfe
Solution structure of meucin-24
Structural highlights
Publication Abstract from PubMedPlasmodium falciparum is a pathogen of human malaria which causes millions of deaths per year due to the ever-increasing drug resistance by the parasite, and thus novel antimalarial agents are urgently needed. In this work, we report two cDNA clones from the scorpion Mesobuthus eupeus venom gland, which encode peptides inhibiting the development of Plasmodium berghei, killing intraerythrocytic P. falciparum, and toxic to the Drosophila S2 cell at micromolar concentrations. One peptide of 24 amino acids (named meucin-24) shares high sequence identity to the amino-terminus of a family of scorpion venom long-chain K(+) channel toxins (LcKTx) and two frog antimicrobial peptides (magainin1 and 2). Sequencing genomic DNA of meucin-24 identified this short peptide as a product of a putative guanine-to-adenine RNA editing from a M. eupeus LcKTx transcript. Another peptide, named meucin-25, contains 25 residues and does not share sequence similarity with any known peptides. Circular dichroism analysis of chemically synthesized peptides demonstrates that meucin-24 presents an essential random coil conformation in water, but its alpha-helical content largely increases in the presence of 50% trifluoroethanol, a membrane-mimicking environment. This finding was further verified by its NMR structure that showed an alpha-helical amphipathic architecture in the region of residues 4-20. CD results indicate that meucin-25 mainly adopts a beta-sheet structure in water but TFE promotes its alpha-helical formation, suggesting its conformational flexibility. Killing of intraerythrocytic P. falciparum without harming mammalian cells (erythrocytes and GC-2 cell) make them attractive candidates for antimalarial drug design. Characterization of two linear cationic antimalarial peptides in the scorpion Mesobuthus eupeus.,Gao B, Xu J, Rodriguez Mdel C, Lanz-Mendoza H, Hernandez-Rivas R, Du W, Zhu S Biochimie. 2010 Apr;92(4):350-9. Epub 2010 Jan 22. PMID:20097251[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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