2YQ7

Structure of Bcl-xL bound to BimLOCK

Summary for 2YQ7

• Entry DOI: 10.2210/pdb2yq7/pdb
• Related: 2YQ6
• Descriptor: BCL-2-LIKE PROTEIN 1, BCL-2-LIKE PROTEIN 11, GLYCEROL, ... (4 entities in total)
• Functional Keywords: constrained peptide, apoptosis, bcl-2 family
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 2
• Total formula weight: 20223.52

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

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: 23151250
DOI: 10.1021/CB3005403

Experimental method

X-RAY DIFFRACTION (1.901 Å)