5AR0

HSP72 with adenosine-derived inhibitor

5AR0 の概要

• エントリーDOI: 10.2210/pdb5ar0/pdb
• 関連するPDBエントリー: 5AQF 5AQG 5AQH 5AQI 5AQJ 5AQK 5AQL 5AQM 5AQN 5AQO 5AQP 5AQQ 5AQR 5AQS 5AQT 5AQU 5AQV 5AQW 5AQX 5AQY 5AQZ
• 分子名称: HEAT SHOCK 70 KDA PROTEIN 1A, (2R,3R,4S,5R)-2-(6-amino-8-((quinolin-7-ylmethyl)amino)-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol, GLYCEROL, ... (6 entities in total)
• 機能のキーワード: heat shock protein, hsp70, hsp72, atpase, chaperone, adenosine, inhibitor
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Cytoplasm : P0DMV8
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 44087.33

構造登録者

Cheeseman, M.D.,Westwood, I.M.,Barbeau, O.,Rowlands, M.G.,Jones, A.M.,Jeganathan, F.,Burke, R.,Dobson, S.E.,Workman, P.,Collins, I.,van Montfort, R.L.M.,Jones, K. (登録日: 2015-09-22, 公開日: 2016-05-11, 最終更新日: 2024-01-10)

主引用文献

Cheeseman, M.D.,Westwood, I.M.,Barbeau, O.,Rowlands, M.G.,Dobson, S.,Jones, A.M.,Jeganathan, F.,Burke, R.,Kadi, N.,Workman, P.,Collins, I.,Van Montfort, R.L.M.,Jones, K.
Exploiting Protein Conformational Change to Optimize Adenosine-Derived Inhibitors of Hsp70.
J.Med.Chem., 59:4625-, 2016

PubMed Abstract: HSP70 is a molecular chaperone and a key component of the heat-shock response. Because of its proposed importance in oncology, this protein has become a popular target for drug discovery, efforts which have as yet brought little success. This study demonstrates that adenosine-derived HSP70 inhibitors potentially bind to the protein with a novel mechanism of action, the stabilization by desolvation of an intramolecular salt-bridge which induces a conformational change in the protein, leading to high affinity ligands. We also demonstrate that through the application of this mechanism, adenosine-derived HSP70 inhibitors can be optimized in a rational manner.

PubMed: 27119979
DOI: 10.1021/ACS.JMEDCHEM.5B02001

実験手法

X-RAY DIFFRACTION (1.9 Å)