2N6M

Structural elucidation of the frog skin-derived peptide Esculentin-1a[Esc(1-21)NH2] inLipopolysaccharide and correlation with their function

Summary for 2N6M

• Entry DOI: 10.2210/pdb2n6m/pdb
• NMR Information: BMRB: 25769
• Descriptor: Esculentin-1A (1 entity in total)
• Functional Keywords: alpha helix, antimicrobial peptide, anti endotoxin peptides, lps, antimicrobial protein
• Biological source: Pelophylax esculentus (Edible frog)
• Total number of polymer chains: 1
• Total formula weight: 2190.74

Authors

Ghosh, A.,Bhunia, A. (deposition date: 2015-08-26, release date: 2016-03-02, Last modification date: 2024-05-15)

Primary citation

Ghosh, A.,Bera, S.,Shai, Y.,Mangoni, M.L.,Bhunia, A.
NMR structure and binding of esculentin-1a (1-21)NH2 and its diastereomer to lipopolysaccharide: Correlation with biological functions
Biochim.Biophys.Acta, 1858:800-812, 2015

PubMed Abstract: The frog skin-derived antimicrobial peptide esculentin-1a(1-21)NH2 [Esc(1-21)], and its diastereomer Esc(1-21)-1c (containing two D-amino acids at positions 14 and 17), have been recently found to neutralize the toxic effect of Pseudomonas aeruginosa lipopolysaccharide (LPS), although to different extents. Here, we studied the three-dimensional structure of both peptides in complex with P. aeruginosa LPS, by transferred nuclear Overhauser effect spectroscopy. Lack of NOE peaks revealed that both the peptides adopted a random coil structure in aqueous solution. However, Esc(1-21) adopted an amphipathic helical conformation in LPS micelles with 5 basic Lys residues forming a hydrophilic cluster. In comparison, the diastereomer maintained an alpha helical conformation only at the N-terminal region, whereas the C-terminal portion was quite flexible. Isothermal titration calorimetry (ITC) revealed that the interaction of Esc(1-21) with LPS is an exothermic process associated with a dissociation constant of -4μM. In contrast, Esc(1-21)-1c had almost 8 times weaker binding affinity to LPS micelles. Moreover, STD NMR data supported by docking analysis have identified those amino acid residues responsible for the peptide's binding to LPS micelles. Overall, the data provide important mechanistic insights on the interaction of esculentin-derived peptides with LPS and the reason for their different anti-endotoxin activity. These data might also assist to further design more potent antimicrobial peptides with antisepsis properties, which are highly needed to overcome the widespread concern of the available anti-infective agents.

PubMed: 26724203
DOI: 10.1016/j.bbamem.2015.12.027

Experimental method

SOLUTION NMR