6g4i

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== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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The emergence of strains of the human pathogen Candida albicans with resistance to commonly used antibiotics has necessitated a search for new types of antifungal agents. Six peptides with antimicrobial activity were isolated from norepinephrine-stimulated skin secretions from the foothill yellow-legged frog Rana boylii. Brevinin-1BYa (FLPILASLAA10KFGPKLF CLV20TKKC) was particularly potent against C. albicans [minimal inhibitory concentration (MIC) = 3 microm] and also active against Escherichia coli (MIC = 17 microm) and Staphylococcus aureus (MIC = 2 microm), but its therapeutic potential for systemic use is limited by its strong hemolytic activity (HC50 = 4 microm). The single amino acid substitution (Phe12 --&gt; Leu) in brevinin-1BYb resulted in a fourfold lower potency against C. albicans and the additional amino acid substitutions (Lys11 --&gt; Thr, Phe17 --&gt; Leu and Val20 --&gt; Ile) in brevinin-1BYc resulted in a ninefold decrease in activity. Two members of the ranatuerin-2 family and one member of the temporin family were also isolated from the secretions but showed relatively low potency against the three microorganisms tested.
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Brevinin-1BYa (FLPILASLAAKFGPKLFCLVTKKC), first isolated from skin secretions of the foothill yellow-legged frog Rana boylii, shows broad-spectrum activity, being particularly effective against opportunistic yeast pathogens. The structure of brevinin-1BYa was investigated in various solution and membrane-mimicking environments by proton nuclear magnetic resonance ((1) H-NMR) spectroscopy and molecular modelling. The peptide does not possess a secondary structure in aqueous solution. In a 33% 2,2,2-trifluoroethanol (TFE-d3 )-H2 O solvent mixture, as well as in membrane-mimicking sodium dodecyl sulfate and dodecylphosphocholine micelles, the peptide's structure is characterised by a flexible helix-hinge-helix motif, with the hinge located at the Gly(13) /Pro(14) residues, and the two alpha-helices extending from Pro(3) to Phe(12) and from Pro(14) to Thr(21) . Positional studies involving the peptide in sodium dodecyl sulfate and dodecylphosphocholine micelles using 5-doxyl-labelled stearic acid and manganese chloride paramagnetic probes show that the peptide's helical segments lie parallel to the micellar surface, with the residues on the hydrophobic face of the amphipathic helices facing towards the micelle core and the hydrophilic residues pointing outwards, suggesting that the peptide exerts its biological activity by a non-pore-forming mechanism.
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Isolation of peptides of the brevinin-1 family with potent candidacidal activity from the skin secretions of the frog Rana boylii.,Conlon JM, Sonnevend A, Patel M, Davidson C, Nielsen PF, Pal T, Rollins-Smith LA J Pept Res. 2003 Nov;62(5):207-13. PMID:14531844<ref>PMID:14531844</ref>
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Structural and positional studies of the antimicrobial peptide brevinin-1BYa in membrane-mimetic environments.,Timmons PB, O'Flynn D, Conlon JM, Hewage CM J Pept Sci. 2019 Nov;25(11):e3208. doi: 10.1002/psc.3208. PMID:31721374<ref>PMID:31721374</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

Revision as of 08:40, 27 November 2019

The solution NMR structure of brevinin-1BYa in 33% trifluoroethanol

PDB ID 6g4i

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