4N84: Crystal Structure Of 14-3-3zeta In Complex With A 12-carbon-linker Cyclic Peptide Derived From Exos

Bioactive conformations of peptides can be stabilized by macrocyclization, resulting in increased target affinity and activity. Such macrocyclic peptides proved useful as modulators of biological functions, in particular as inhibitors of protein-protein interactions (PPI). However, most peptide-derived PPI inhibitors involve stabilized alpha-helices, leaving a large number of secondary structures unaddressed. Herein, we present a rational approach towards stabilization of an irregular peptide structure, using hydrophobic cross-links that replace residues crucially involved in target binding. The molecular basis of this interaction was elucidated by X-ray crystallography and isothermal titration calorimetry. The resulting cross-linked peptides inhibit the interaction between human adaptor protein 14-3-3 and virulence factor exoenzyme S. Taking into consideration that irregular peptide structures participate widely in PPIs, this approach provides access to novel peptide-derived inhibitors.
PDB ID: 4N84Download
MMDB ID: 117682
PDB Deposition Date: 2013/10/17
Updated in MMDB: 2014/03
Experimental Method:
x-ray diffraction
Resolution: 2.5  Å
Source Organism:
Homo sapiens
Similar Structures:
Biological Unit for 4N84: tetrameric; determined by author and by software (PISA)
Molecular Components in 4N84
Label Count Molecule
Proteins (4 molecules)
14-3-3 Protein Zeta/delta(Gene symbol: YWHAZ)
Molecule annotation
Exoenzyme S
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB