8AN9

Fucosylated mixed-chirality linear peptide FHP5 bound to the fucose binding lectin LecB PA-IIL from Pseudomonas aeruginosa at 1.3 Angstrom resolution.

これはPDB形式変換不可エントリーです。

8AN9 の概要

• エントリーDOI: 10.2210/pdb8an9/pdb
• 分子名称: Fucose-binding lectin PA-IIL, Mixed-chirality peptide FHP5, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: antimicrobial peptide, alpha helix, mixed-chirality, antibiotic
• 由来する生物種: Pseudomonas aeruginosa PAO1; 詳細
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 52055.74

構造登録者

Personne, H.,Stocker, A.,Reymond, J.-L. (登録日: 2022-08-04, 公開日: 2023-05-31, 最終更新日: 2024-10-23)

主引用文献

Personne, H.,Paschoud, T.,Fulgencio, S.,Baeriswyl, S.,Kohler, T.,van Delden, C.,Stocker, A.,Javor, S.,Reymond, J.L.
To Fold or Not to Fold: Diastereomeric Optimization of an alpha-Helical Antimicrobial Peptide.
J.Med.Chem., 66:7570-7583, 2023

PubMed Abstract: Membrane disruptive α-helical antimicrobial peptides (AMPs) offer an opportunity to address multidrug resistance; however, most AMPs are toxic and unstable in serum. These limitations can be partly overcome by introducing D-residues, which often confers protease resistance and reduces toxicity without affecting antibacterial activity, presumably due to lowered α-helicity. Here, we investigated 31 diastereomers of the α-helical AMP KKLLKLLKLLL. Three diastereomers containing two, three, and four D-residues showed increased antibacterial effects, comparable hemolysis, reduced toxicity against HEK293 cells, and excellent serum stability, while another diastereomer with four D-residues additionally displayed lower hemolysis. X-ray crystallography confirmed that high or low α-helicity as measured by circular dichroism indicated α-helical or disordered structures independently of the number of chirality switched residues. In contrast to previous reports, α-helicity across diastereomers correlated with both antibacterial activity and hemolysis and revealed a complex relationship between stereochemistry, activity, and toxicity, highlighting the potential of diastereomers for property optimization.

PubMed: 37227046
DOI: 10.1021/acs.jmedchem.3c00460

実験手法

X-RAY DIFFRACTION (1.273 Å)