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Publication Abstract from PubMed

Herein, we report X-ray crystal structures of 11-13 residue antimicrobial peptides (AMPs) active against Pseudomonas aeruginosa as complexes of fucosylated d-enantiomeric sequences with the P. aeruginosa lectin LecB. These represent the first crystal structures of short AMPs. In 24 individual structures of eight different peptides, we found mostly alpha-helices assembled as two-helix or four-helix bundles with a hydrophobic core and cationic residues pointing outside. Two of the analogs formed an extended structure engaging in multiple contacts with the lectin. Molecular dynamics (MD) simulations showed that alpha-helices are stabilized by bundle formation and suggested that the N-terminal acyl group present in the linker to the fucosyl group can extend the helix by one additional H-bond and increase alpha-helix amphiphilicity. Investigating N-terminal acylation led to AMPs with equivalent and partly stronger antibacterial effects compared to the free peptide.

X-ray Crystal Structures of Short Antimicrobial Peptides as Pseudomonas aeruginosa Lectin B Complexes.,Baeriswyl S, Gan BH, Siriwardena TN, Visini R, Robadey M, Javor S, Stocker A, Darbre T, Reymond JL ACS Chem Biol. 2019 Mar 11. doi: 10.1021/acschembio.9b00047. PMID:30830745^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.