PDBsum entry 6q8h

Antibiotic

PDB id: 6q8h

Contents

Protein chain

114 a.a.

Ligands

DLE-DLE-DLY-DAL-DLE-DLY-DLY-DLE-DAL-DLY-DLY-DTY-DLY ×2

ZDC ×2

NH2 ×2

Metals

_CA ×2

Waters ×177

References listed in PDB file

Key reference

• Title: X-Ray crystal structures of short antimicrobial peptides as pseudomonas aeruginosa lectin b complexes.
• Authors: S.Baeriswyl, B.H.Gan, T.N.Siriwardena, R.Visini, M.Robadey, S.Javor, A.Stocker, T.Darbre, J.L.Reymond.
• Ref.: ACS Chem Biol, 2019, 14, 758-766. [DOI no: 10.1021/acschembio.9b00047]
• PubMed id: 30830745

Abstract

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 α-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 α-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 α-helix amphiphilicity. Investigating N-terminal acylation led to AMPs with equivalent and partly stronger antibacterial effects compared to the free peptide.