PDBsum entry 2kfe

Antimicrobial protein

PDB id: 2kfe

Contents

Protein chain

24 a.a.

PDB id:

2kfe

Name:

Antimicrobial protein

Title:

Solution structure of meucin-24

Structure:

Meucin-24. Chain: a. Engineered: yes

Source:

Synthetic: yes. Other_details: chemically synthesized

NMR struc:

20 models

Authors:

W.Du,J.Xu,B.Gao,S.Zhu

Key ref:

B.Gao et al. (2010). Characterization of two linear cationic antimalarial peptides in the scorpion Mesobuthus eupeus. Biochimie, 92, 350-359. PubMed id: 20097251

Date:

18-Feb-09 Release date: 26-Jan-10

Protein chain

No UniProt id for this chain

Struc: 24 a.a.

Biochimie 92:350-359 (2010)

PubMed id: 20097251

Characterization of two linear cationic antimalarial peptides in the scorpion Mesobuthus eupeus.

B.Gao, J.Xu, M.d.e.l. .C.Rodriguez, H.Lanz-Mendoza, R.Hernández-Rivas, W.Du, S.Zhu.

ABSTRACT

Plasmodium 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.