X-ray Crystal Structures of Short Antimicrobial Peptides as Pseudomonas aeruginosa Lectin B Complexes.
ACS Chem Biol
; 14(4): 758-766, 2019 04 19.
Article
em En
| MEDLINE
| ID: mdl-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.
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Base de dados:
MEDLINE
Assunto principal:
Pseudomonas aeruginosa
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Proteínas de Bactérias
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Peptídeos Catiônicos Antimicrobianos
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Lectinas
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Anti-Infecciosos
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article