4IEH

Crystal Structure of human Bcl-2 in complex with a small molecule inhibitor targeting Bcl-2 BH3 domain interactions

4IEH の概要

• エントリーDOI: 10.2210/pdb4ieh/pdb
• 分子名称: Apoptosis regulator Bcl-2, Bcl-2-like protein 1 chimera, N-(6-{4-[(4'-chlorobiphenyl-2-yl)methyl]piperazin-1-yl}-1,1-dioxido-1,2-benzothiazol-3-yl)-4-{[(2R)-4-(dimethylamino)-1-(phenylsulfanyl)butan-2-yl]amino}-3-nitrobenzenesulfonamide (3 entities in total)
• 機能のキーワード: protein-protein interaction, alpha helical, pro-apoptosis, cytochrome c release, caspase activation, bim, bak, bad, puma, apoptosis-inhibitor complex, apoptosis/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: 1
• 化学式量合計: 20514.32

構造登録者

Xie, X.,Kulathila, R. (登録日: 2012-12-13, 公開日: 2013-07-10, 最終更新日: 2024-02-28)

主引用文献

Toure, B.B.,Miller-Moslin, K.,Yusuff, N.,Perez, L.,Dore, M.,Joud, C.,Michael, W.,DiPietro, L.,van der Plas, S.,McEwan, M.,Lenoir, F.,Hoe, M.,Karki, R.,Springer, C.,Sullivan, J.,Levine, K.,Fiorilla, C.,Xie, X.,Kulathila, R.,Herlihy, K.,Porter, D.,Visser, M.
The role of the acidity of N-heteroaryl sulfonamides as inhibitors of bcl-2 family protein-protein interactions.
ACS Med Chem Lett, 4:186-190, 2013

PubMed Abstract: Overexpression of the antiapoptotic members of the Bcl-2 family of proteins is commonly associated with cancer cell survival and resistance to chemotherapeutics. Here, we describe the structure-based optimization of a series of N-heteroaryl sulfonamides that demonstrate potent mechanism-based cell death. The role of the acidic nature of the sulfonamide moiety as it relates to potency, solubility, and clearance is examined. This has led to the discovery of novel heterocyclic replacements for the acylsulfonamide core of ABT-737 and ABT-263.

PubMed: 24900652
DOI: 10.1021/ml300321d

実験手法

X-RAY DIFFRACTION (2.1 Å)