X-ray Crystal Structures of Short Antimicrobial Peptides as Pseudomonas aeruginosa Lectin B Complexes.

Autor:	Baeriswyl S; Department of Chemistry and Biochemistry , University of Bern , Freiestrasse 3 , 3012 Bern , Switzerland., Gan BH; Department of Chemistry and Biochemistry , University of Bern , Freiestrasse 3 , 3012 Bern , Switzerland., Siriwardena TN; Department of Chemistry and Biochemistry , University of Bern , Freiestrasse 3 , 3012 Bern , Switzerland., Visini R; Department of Chemistry and Biochemistry , University of Bern , Freiestrasse 3 , 3012 Bern , Switzerland., Robadey M; Department of Chemistry and Biochemistry , University of Bern , Freiestrasse 3 , 3012 Bern , Switzerland., Javor S; Department of Chemistry and Biochemistry , University of Bern , Freiestrasse 3 , 3012 Bern , Switzerland., Stocker A; Department of Chemistry and Biochemistry , University of Bern , Freiestrasse 3 , 3012 Bern , Switzerland., Darbre T; Department of Chemistry and Biochemistry , University of Bern , Freiestrasse 3 , 3012 Bern , Switzerland., Reymond JL; Department of Chemistry and Biochemistry , University of Bern , Freiestrasse 3 , 3012 Bern , Switzerland.
Jazyk:	angličtina
Zdroj:	ACS chemical biology [ACS Chem Biol] 2019 Apr 19; Vol. 14 (4), pp. 758-766. Date of Electronic Publication: 2019 Mar 11.
DOI:	10.1021/acschembio.9b00047
Abstrakt:	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.
Databáze:	MEDLINE
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