2ln4
From Proteopedia
Insight into the antimicrobial activities based on the Structure-activity relationships of coprisin isolated from the Dung Beetle, Copris tripartitus
Structural highlights
FunctionDEF_COPTR Potent broad-spectrum antibacterial peptide against both Gram-positive (B.subtilis, S.epidermidis, and S.aureus) and Gram-negative bacteria (E.coli, S.typhimurium, and P.aeruginosa) (PubMed:20721297, PubMed:23137439). Is also active against all antibiotic-resistant bacterial strains tested (PubMed:23137439). Induces apoptosis in C.albicans, but does not disrupt the fungal plasma membrane at all (PubMed:22542795). Acts by permeabilizing the bacterial cell membrane, but not human membranes (PubMed:23137439). Also shows potent anti-inflammatory activities, since it reduces both LPS-induced nitric oxide release and pro-inflammatory cytokine production (PubMed:23137439). Anti-inflammatory activities are initiated by suppressing the binding of LPS to toll-like receptor 4 (TLR4), and subsequently inhibiting the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and nuclear translocation of NF-kB (TNFRSF11A) (PubMed:23137439). Does not show hemolytic activity against human erythrocytes (PubMed:23137439).[1] [2] [3] Publication Abstract from PubMedThe novel 43-residue, insect defensin-like peptide coprisin, isolated from the dung beetle, Copris tripartitus, is a potent antibiotic with bacterial cell selectivity, exhibiting antimicrobial activities against Gram-positive and Gram-negative bacteria without exerting hemolytic activity against human erythrocytes. Tests against Staphylococcus aureus using fluorescent dye leakage and depolarization measurements showed that coprisin targets the bacterial cell membrane. To understand structure-activity relationships, we determined the three-dimensional structure of coprisin in aqueous solution by nuclear magnetic resonance spectroscopy, which showed that coprisin has an amphipathic alpha-helical structure from Ala(19) to Arg(28), and beta-sheets from Gly(31) to Gln(35) and Val(38) to Arg(42). Coprisin has electropositive regions formed by Arg(28), Lys(29), Lys(30), and Arg(42) and ITC results proved that coprisin and LPS have electrostatically driven interactions. Using measurements of nitric oxide release and inflammatory cytokine production, we provide the first verification of the anti-inflammatory activity and associated mechanism of an insect defensin, demonstrating that the anti-inflammatory actions of the defensin-like peptide, coprisin, are initiated by suppressing the binding of LPS to toll-like receptor 4, and subsequently inhibiting the phosphorylation of p38 mitogen-activated protein kinase and nuclear translocation of NF-kB. In conclusion, we have demonstrated that an amphipathic helix and an electropositive surface in coprisin may play important roles in its effective interaction with bacterial cell membranes and, ultimately, in its high antibacterial activity and potent anti-inflammatory activity. In addition to elucidating the antimicrobial action of coprisin, this work may provide insight into the mechanism of action of insect defense systems. Insight into the antimicrobial activities of coprisin isolated from the dung beetle, Copris tripartitus, revealed by structure-activity relationships.,Lee E, Kim JK, Shin S, Jeong KW, Shin A, Lee J, Lee DG, Hwang JS, Kim Y Biochim Biophys Acta. 2012 Nov 6. pii: S0005-2736(12)00377-X. doi:, 10.1016/j.bbamem.2012.10.028. PMID:23137439[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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