5JM4
Crystal structure of 14-3-3zeta in complex with a cyclic peptide involving an adamantyl and a dicarboxy side chain
Summary for 5JM4
| Entry DOI | 10.2210/pdb5jm4/pdb |
| Related | 4N7G 4N84 |
| Descriptor | 14-3-3 protein zeta/delta, GLN-GLY-MKD-ANG-ASP-MKD-LEU-ASP-LEU-ALA-CLU, BENZOIC ACID, ... (4 entities in total) |
| Functional Keywords | peptidomimetic, ppi inhibitor, macrocycle, signaling protein |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 55687.07 |
| Authors | Bier, D.,Krueger, D.,Glas, A.,Wallraven, K.,Ottmann, C.,Hennig, S.,Grossmann, T. (deposition date: 2016-04-28, release date: 2017-05-10, Last modification date: 2024-01-10) |
| Primary citation | Kruger, D.M.,Glas, A.,Bier, D.,Pospiech, N.,Wallraven, K.,Dietrich, L.,Ottmann, C.,Koch, O.,Hennig, S.,Grossmann, T.N. Structure-Based Design of Non-natural Macrocyclic Peptides That Inhibit Protein-Protein Interactions. J. Med. Chem., 60:8982-8988, 2017 Cited by PubMed Abstract: Macrocyclic peptides can interfere with challenging biomolecular targets including protein-protein interactions. Whereas there are various approaches that facilitate the identification of peptide-derived ligands, their evolution into higher affinity binders remains a major hurdle. We report a virtual screen based on molecular docking that allows the affinity maturation of macrocyclic peptides taking non-natural amino acids into consideration. These macrocycles bear large and flexible substituents that usually complicate the use of docking approaches. A virtual library containing more than 1400 structures was screened against the target focusing on docking poses with the core structure resembling a known bioactive conformation. Based on this screen, a macrocyclic peptide 22 involving two non-natural amino acids was evolved showing increased target affinity and biological activity. Predicted binding modes were verified by X-ray crystallography. The presented workflow allows the screening of large macrocyclic peptides with diverse modifications thereby expanding the accessible chemical space and reducing synthetic efforts. PubMed: 29028171DOI: 10.1021/acs.jmedchem.7b01221 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.34 Å) |
Structure validation
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