2YQ7

Structure of Bcl-xL bound to BimLOCK

2YQ7 の概要

• エントリーDOI: 10.2210/pdb2yq7/pdb
• 関連するPDBエントリー: 2YQ6
• 分子名称: BCL-2-LIKE PROTEIN 1, BCL-2-LIKE PROTEIN 11, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: constrained peptide, apoptosis, bcl-2 family
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 20223.52

構造登録者

Smith, B.J.,Czabotar, P.E. (登録日: 2012-11-06, 公開日: 2012-11-28, 最終更新日: 2024-11-13)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.901 Å)