5AQZ

HSP72 with adenosine-derived inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.65 Å
  • R-Value Free: 0.221 
  • R-Value Work: 0.186 
  • R-Value Observed: 0.188 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Exploiting Protein Conformational Change to Optimize Adenosine-Derived Inhibitors of Hsp70.

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.

(2016) J Med Chem 59: 4625

  • DOI: https://doi.org/10.1021/acs.jmedchem.5b02001
  • Primary Citation of Related Structures:  
    5AQZ, 5AR0

  • 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.


  • Organizational Affiliation

    Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research , London SW7 3RP, U.K.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HEAT SHOCK 70 KDA PROTEIN 1A394Homo sapiensMutation(s): 0 
EC: 3.6.3.51
UniProt & NIH Common Fund Data Resources
Find proteins for P0DMV8 (Homo sapiens)
Explore P0DMV8 
Go to UniProtKB:  P0DMV8
PHAROS:  P0DMV8
GTEx:  ENSG00000204389 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP0DMV8
Sequence Annotations
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  • Reference Sequence
Small Molecules
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.65 Å
  • R-Value Free: 0.221 
  • R-Value Work: 0.186 
  • R-Value Observed: 0.188 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 47.938α = 90
b = 89.504β = 90
c = 96.92γ = 90
Software Package:
Software NamePurpose
BUSTERrefinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2016-05-11
    Type: Initial release
  • Version 1.1: 2016-06-08
    Changes: Database references
  • Version 1.2: 2024-01-10
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description