2YQ6
Structure of Bcl-xL bound to BimSAHB
Summary for 2YQ6
Entry DOI | 10.2210/pdb2yq6/pdb |
Related | 2YQ7 |
Descriptor | BCL-2-LIKE PROTEIN 1, BIM BETA 5, GLYCEROL, ... (4 entities in total) |
Functional Keywords | constrained peptide, apoptosis, bcl-2 family |
Biological source | HOMO SAPIENS (HUMAN) More |
Cellular location | Mitochondrion membrane; Single-pass membrane protein: Q07817 Endomembrane system; Peripheral membrane protein (By similarity). Isoform BimEL: Mitochondrion. Isoform BimL: Mitochondrion. Isoform BimS: Mitochondrion. Isoform Bim-alpha1: Mitochondrion: O43521 |
Total number of polymer chains | 2 |
Total formula weight | 20746.12 |
Authors | Smith, B.J.,Czabotar, P.E. (deposition date: 2012-11-06, release date: 2012-11-28, Last modification date: 2024-11-13) |
Primary citation | Okamoto, T.,Zobel, K.,Fedorova, A.,Quan, C.,Yang, H.,Fairbrother, W.J.,Huang, D.C.S.,Smith, B.J.,Deshayes, K.,Czabotar, P.E. Stabilizing the Pro-Apoptotic Bimbh3 Helix (Bimsahb) Does not Necessarily Enhance Affinity or Biological Activity. Acs Chem.Biol., 8:297-, 2013 Cited by PubMed Abstract: An attractive approach for developing therapeutic peptides is to enhance binding to their targets by stabilizing their α-helical conformation, for example, stabilized BimBH3 peptides (BimSAHB) designed to induce apoptosis. Unexpectedly, we found that such modified peptides have reduced affinity for their targets, the pro-survival Bcl-2 proteins. We attribute this loss in affinity to disruption of a network of stabilizing intramolecular interactions present in the bound state of the native peptide. Altering this network may compromise binding affinity, as in the case of the BimBH3 stapled peptide studied here. Moreover, cells exposed to these peptides do not readily undergo apoptosis, strongly indicating that BimSAHB is not inherently cell permeable. PubMed: 23151250DOI: 10.1021/CB3005403 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.799 Å) |
Structure validation
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