5J31

Crystal structure of 14-3-3zeta in complex with an alkyne cross-linked cyclic peptide derived from ExoS

Summary for 5J31

• Entry DOI: 10.2210/pdb5j31/pdb
• Related: 4N7G 4N7Y 4N84
• Descriptor: 14-3-3 protein zeta/delta, Exoenzyme S, BENZOIC ACID, ... (4 entities in total)
• Functional Keywords: constrained peptides, protein-protein-interaction, alkyne cross-link, 14-3-3 protein zeta, signaling protein
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm : P63104
• Total number of polymer chains: 4
• Total formula weight: 54974.28

Authors

Wallraven, K.,Cromm, P.,Bier, D.,Glas, A.,Grossmann, T. (deposition date: 2016-03-30, release date: 2016-10-19, Last modification date: 2024-11-20)

Primary citation

Cromm, P.M.,Wallraven, K.,Glas, A.,Bier, D.,Furstner, A.,Ottmann, C.,Grossmann, T.N.
Constraining an Irregular Peptide Secondary Structure through Ring-Closing Alkyne Metathesis.
Chembiochem, 17:1915-1919, 2016

PubMed Abstract: Macrocyclization can be used to constrain peptides in their bioactive conformations, thereby supporting target affinity and bioactivity. In particular, for the targeting of challenging protein-protein interactions, macrocyclic peptides have proven to be very useful. Available approaches focus on the stabilization of α-helices, which limits their general applicability. Here we report for the first time on the use of ring-closing alkyne metathesis for the stabilization of an irregular peptide secondary structure. A small library of alkyne-crosslinked peptides provided a number of derivatives with improved target affinity relative to the linear parent peptide. In addition, we report the crystal structure of the highest-affinity derivative in a complex with its protein target 14-3-3ζ. It can be expected that the alkyne-based macrocyclization of irregular binding epitopes should give rise to new scaffolds suitable for targeting of currently intractable proteins.

PubMed: 27596722
DOI: 10.1002/cbic.201600362

Experimental method

X-RAY DIFFRACTION (2.4 Å)