Engineered conjugation of lysine-specific molecular tweezers with exos derived peptidic inhibitor enhance affinity towards target protein 14-3-3 through ditopic binding

Structure

x-ray diffraction · 4 distinct chains · 78% helix, 0% strand (DSSP).

Ligands and binding sites

• TWZ · ExoSTWZ molecular tweezer · ligand · 2 copies · chains A, D, F, E
• NA · Sodium ion · metal · 5 copies · chains A, F, P, K
• GOL · Glycerol · additive · 2 copies · chains A, K, P

Binding sites are the residues within 4.5 Å of a ligand's heavy atoms.

Pockets

10 pockets found on a 1 Å grid, 1 with a druggability of 0.5 or more.

Interfaces

5 interfaces between chains.

• F–P · 1067 Ų buried · 12 hydrogen bonds · protein-protein
• A–E · 744 Ų buried · 7 hydrogen bonds · protein-protein
• D–F · 689 Ų buried · 10 hydrogen bonds · protein-protein
• A–F · 558 Ų buried · 2 hydrogen bonds · protein-protein
• A–K · 255 Ų buried · 2 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 4 modified, 2 covalent (oxidation, covalent ligand).

Compared structures

• 6Y7T · Engineered conjugation of lysine-specific molecular tweezers with ExoS derived peptidic… · the same entry in another collection · chain P against P, TM-score 1.00
• P31947 · AlphaFold monomer V2.0 prediction for 14-3-3 protein sigma (P31947) · a predicted model of the same protein · chain K against A, TM-score 0.96

Analyse

• Open in the research workbench: secondary structure, accessibility, pockets, interfaces, conservation, variants, modifications, peptides and crosslinks on the 3D structure
• Every structure of UniProt P31947
• Every structure of UniProt Q51451
• Elsewhere: RCSB PDB 6Y7T · PDBe 6Y7T · UniProt P31947 · UniProt Q51451