5AR0

HSP72 with adenosine-derived inhibitor

Summary for 5AR0

• Entry DOI: 10.2210/pdb5ar0/pdb
• Related: 5AQF 5AQG 5AQH 5AQI 5AQJ 5AQK 5AQL 5AQM 5AQN 5AQO 5AQP 5AQQ 5AQR 5AQS 5AQT 5AQU 5AQV 5AQW 5AQX 5AQY 5AQZ
• Descriptor: 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)
• Functional Keywords: heat shock protein, hsp70, hsp72, atpase, chaperone, adenosine, inhibitor
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm : P0DMV8
• Total number of polymer chains: 1
• Total formula weight: 44087.33

Authors

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. (deposition date: 2015-09-22, release date: 2016-05-11, Last modification date: 2024-01-10)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.9 Å)