5JSN

Bcl2-inhibitor complex

5JSN の概要

• エントリーDOI: 10.2210/pdb5jsn/pdb
• 関連するPDBエントリー: 4OYD 5JSB
• 分子名称: Apoptosis regulator Bcl-2, Bcl2 inhibitor (3 entities in total)
• 機能のキーワード: bcl-2, antibcl2, complex, viral protein-inhibitor complex, viral protein/inhibitor
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Mitochondrion outer membrane ; Single-pass membrane protein : P10415
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 75575.60

構造登録者

Shen, B.W.,Stoddard, B.L. (登録日: 2016-05-09, 公開日: 2016-11-16, 最終更新日: 2024-03-06)

主引用文献

Berger, S.,Procko, E.,Margineantu, D.,Lee, E.F.,Shen, B.W.,Zelter, A.,Silva, D.A.,Chawla, K.,Herold, M.J.,Garnier, J.M.,Johnson, R.,MacCoss, M.J.,Lessene, G.,Davis, T.N.,Stayton, P.S.,Stoddard, B.L.,Fairlie, W.D.,Hockenbery, D.M.,Baker, D.
Computationally designed high specificity inhibitors delineate the roles of BCL2 family proteins in cancer.
Elife, 5:-, 2016

PubMed Abstract: Many cancers overexpress one or more of the six human pro-survival BCL2 family proteins to evade apoptosis. To determine which BCL2 protein or proteins block apoptosis in different cancers, we computationally designed three-helix bundle protein inhibitors specific for each BCL2 pro-survival protein. Following in vitro optimization, each inhibitor binds its target with high picomolar to low nanomolar affinity and at least 300-fold specificity. Expression of the designed inhibitors in human cancer cell lines revealed unique dependencies on BCL2 proteins for survival which could not be inferred from other BCL2 profiling methods. Our results show that designed inhibitors can be generated for each member of a closely-knit protein family to probe the importance of specific protein-protein interactions in complex biological processes.

PubMed: 27805565
DOI: 10.7554/eLife.20352

実験手法

X-RAY DIFFRACTION (2.1 Å)