3FZL

Crystal Structures of Hsc70/Bag1 in Complex with Small Molecule Inhibitors

3FZL の概要

• エントリーDOI: 10.2210/pdb3fzl/pdb
• 関連するPDBエントリー: 3FZF 3FZH 3FZK 3FZM
• 分子名称: Heat shock cognate 71 kDa protein, BAG family molecular chaperone regulator 1, 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ... (5 entities in total)
• 機能のキーワード: hsp70, hsc70, bag1, heat shock, chaperone, protein folding, adenosine, nucleotide, nucleotide exchange factor, small molecule inhibitor, atp-binding, nucleotide-binding, stress response, apoptosis
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cytoplasm: P11142; Isoform 1: Nucleus. Isoform 2: Cytoplasm. Isoform 4: Cytoplasm: Q99933
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 55922.26

構造登録者

Dokurno, P.,Williamson, D.S.,Murray, J.B.,Surgenor, A.E. (登録日: 2009-01-26, 公開日: 2009-03-17, 最終更新日: 2024-10-30)

主引用文献

Williamson, D.S.,Borgognoni, J.,Clay, A.,Daniels, Z.,Dokurno, P.,Drysdale, M.J.,Foloppe, N.,Francis, G.L.,Graham, C.J.,Howes, R.,Macias, A.T.,Murray, J.B.,Parsons, R.,Shaw, T.,Surgenor, A.E.,Terry, L.,Wang, Y.,Wood, M.,Massey, A.J.
Novel adenosine-derived inhibitors of 70 kDa heat shock protein, discovered through structure-based design
J.Med.Chem., 52:1510-1513, 2009

PubMed Abstract: The design and synthesis of novel adenosine-derived inhibitors of HSP70, guided by modeling and X-ray crystallographic structures of these compounds in complex with HSC70/BAG-1, is described. Examples exhibited submicromolar affinity for HSP70, were highly selective over HSP90, and some displayed potency against HCT116 cells. Exposure of compound 12 to HCT116 cells caused significant reduction in cellular levels of Raf-1 and Her2 at concentrations similar to that which caused cell growth arrest.

PubMed: 19256508
DOI: 10.1021/jm801627a

実験手法

X-RAY DIFFRACTION (2.2 Å)