8ANR
Fucosylated alternate chirality linear peptide FHP30 bound to the fucose binding lectin LecB PA-IIL from Pseudomonas aeruginosa at 1.6 Angstrom resolution.
Summary for 8ANR
| Entry DOI | 10.2210/pdb8anr/pdb |
| Descriptor | Fucose-binding lectin PA-IIL, Fucosylated mixed-chirality linear peptide FHP30, CALCIUM ION, ... (5 entities in total) |
| Functional Keywords | antimicrobial peptide, alpha helix, mixed-chirality, fucose-binding lectin, antibiotic |
| Biological source | Pseudomonas aeruginosa PAO1 More |
| Total number of polymer chains | 4 |
| Total formula weight | 26687.78 |
| Authors | Personne, H.,Stocker, A.,Reymond, J.-L. (deposition date: 2022-08-05, release date: 2023-05-31, Last modification date: 2024-02-07) |
| Primary citation | 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 Cited by 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: 37227046DOI: 10.1021/acs.jmedchem.3c00460 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.62 Å) |
Structure validation
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