Helical Hairpin Structure of a Potent Antimicrobial Peptide MSI-594 in Lipopolysaccharide Micelles by NMR Spectroscopy

Three dimensional (3D) helical hairpin structure of a highly active antimicrobial peptide MSI-594 in lipopolysaccharide (LPS) micelles using transferred nuclear Overhauser effect (Tr-NOE) or exchanged transferred nuclear Overhauser effect (Et-NOE) spectroscopy was presented. The hybrid MSI-594 was derived based on the premise that the cationic N-terminus of MSI-78 provide binding to negatively charged membrane head groups. Medium range NOEs are observed between amide protons of the carboxylic group of residue 1.24 with T21C/H3. The structure and interactions of MSI-594 peptide with LPS provides novel insights into a potent antomicrobial peptide overcoming the LPS barrier. It is also found that the positively charged groups of Lys residues across the two helices maintain a typical distance range of 12 to 15 Å.