6Y14

Bicyclic peptide bp65 crystallized as racemic mixture at 0.9 Angstrom resolution

Summary for 6Y14

• Entry DOI: 10.2210/pdb6y14/pdb
• Descriptor: bp65, CITRIC ACID (3 entities in total)
• Functional Keywords: antimicrobial, bicyclic, stapled, antibiotic
• Biological source: synthetic construct
• Total number of polymer chains: 2
• Total formula weight: 3350.25

Authors

Baeriswyl, S.,Stocker, A.,Reymond, J.-L. (deposition date: 2020-02-11, release date: 2021-02-17, Last modification date: 2024-10-23)

Primary citation

Baeriswyl, S.,Personne, H.,Di Bonaventura, I.,Kohler, T.,van Delden, C.,Stocker, A.,Javor, S.,Reymond, J.L.
A mixed chirality alpha-helix in a stapled bicyclic and a linear antimicrobial peptide revealed by X-ray crystallography.
Rsc Chem Biol, 2:1608-1617, 2021

PubMed Abstract: The peptide α-helix is right-handed when containing amino acids with l-chirality, and left-handed with d-chirality, however mixed chirality peptides generally do not form α-helices unless a helix inducer such as the non-natural residue amino-isobutyric acid is used. Herein we report the first X-ray crystal structures of mixed chirality α-helices in short peptides comprising only natural residues as the example of a stapled bicyclic and a linear membrane disruptive amphiphilic antimicrobial peptide (AMP) containing seven l- and four d-residues, as complexes of fucosylated analogs with the bacterial lectin LecB. The mixed chirality α-helices are superimposable onto the homochiral α-helices and form under similar conditions as shown by CD spectra and MD simulations but non-hemolytic and resistant to proteolysis. The observation of a mixed chirality α-helix with only natural residues in the protein environment of LecB suggests a vast unexplored territory of α-helical mixed chirality sequences and their possible use for optimizing bioactive α-helical peptides.

PubMed: 34977576
DOI: 10.1039/d1cb00124h

Experimental method

X-RAY DIFFRACTION (0.9 Å)