6RJP
Bfl-1 in complex with alpha helical peptide
Summary for 6RJP
| Entry DOI | 10.2210/pdb6rjp/pdb |
| Descriptor | Bcl-2-related protein A1, Bcl-2-like protein 11 (3 entities in total) |
| Functional Keywords | protein-protein interactions, stapled alpha helix, covalent inhibitor, bcl2-2 family proteins, peptide binding protein |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 43226.85 |
| Authors | Baggio, C.,Gambini, L.,Udompholkul, P.,Salem, A.F.,Hakansson, M.,Jossart, J.,Perry, J.,Pellecchia, M. (deposition date: 2019-04-29, release date: 2019-10-30, Last modification date: 2024-01-24) |
| Primary citation | Baggio, C.,Udompholkul, P.,Gambini, L.,Jossart, J.,Salem, A.F.,Hakansson, M.,Perry, J.J.P.,Pellecchia, M. N-locking stabilization of covalent helical peptides: Application to Bfl-1 antagonists. Chem.Biol.Drug Des., 95:412-426, 2020 Cited by PubMed Abstract: Recently, it was reported that tetrapeptides cyclized via lactam bond between the amino terminus and a glutamic residue in position 4 (termed here N-lock) can nucleate helix formation in longer peptides. We applied such strategy to derive N-locked covalent BH3 peptides that were designed to selectively target the anti-apoptotic protein Bfl-1. The resulting agents were soluble in aqueous buffer and displayed a remarkable (low nanomolar) affinity for Bfl-1 and cellular activity. The crystal structure of the complex between such N-locked covalent peptide and Bfl-1 provided insights on the geometry of the N-locking strategy and of the covalent bond between the agent and Bfl-1. PubMed: 31898401DOI: 10.1111/cbdd.13661 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.57 Å) |
Structure validation
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