Conformational analysis of the broad-spectrum antibacterial peptide, ranatuerin-2CSa: Identification of a full length helix-turn-helix motif

Anusha P. Subasinghage, J. Michael Conlon, Chandralal M. Hewage

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

Design of clinically valuable antibacterial agents based upon naturally occurring peptides requires the use of spectroscopic methods, particularly NMR, to determine the three-dimensional structure of the native peptide so that analogues with improved therapeutic properties can be made. Ranatuerin-2CSa (GILSSFKGVAKGVAKDLAG KLLETLKCKITGC), first isolated from skin secretions of the Cascades frog, Rana cascadae, represents a promising candidate for drug development. The peptide shows potent growth inhibitory activity against Escherichia coli (MIC = 5 μM) and Staphylococcus aureus (MIC = 10 μM) but displays haemolytic activity against human erythrocytes (LC50 = 160 μM). The solution structure of ranatuerin-2CSa was investigated by proton NMR spectroscopy and molecular modelling. In aqueous solution, the peptide lacks secondary structure but, in a 2,2,2-trifluoroethanol (TFE-d3)-H2O solvent mixture, the structure is characterised by a full length helix-turn-helix conformation between residues I2-L21, L22-L25 and K26-T30 respectively. This structural information will facilitate the design of novel therapeutic agents based upon the ranatuerin-2CSa structure with improved antimicrobial potencies but decreased cytolytic activities against mammalian cells.

Original languageEnglish
Pages (from-to)924-929
Number of pages6
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1784
Issue number6
DOIs
Publication statusPublished - Jun 2008
Externally publishedYes

Keywords

  • Antimicrobial
  • Molecular modelling
  • NMR
  • Ranatuerin-2

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biophysics
  • Biochemistry
  • Molecular Biology

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