4EGK

Human Hsp90-alpha ATPase domain bound to Radicicol


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.69 Å
  • R-Value Free: 0.243 
  • R-Value Work: 0.201 
  • R-Value Observed: 0.203 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Fragment screening using capillary electrophoresis (CEfrag) for hit identification of heat shock protein 90 ATPase inhibitors.

Austin, C.Pettit, S.N.Magnolo, S.K.Sanvoisin, J.Chen, W.Wood, S.P.Freeman, L.D.Pengelly, R.J.Hughes, D.E.

(2012) J Biomol Screen 17: 868-876

  • DOI: https://doi.org/10.1177/1087057112445785
  • Primary Citation of Related Structures:  
    4EGH, 4EGI, 4EGK

  • PubMed Abstract: 

    CEfrag is a new fragment screening technology based on affinity capillary electrophoresis (ACE). Here we report on the development of a mobility shift competition assay using full-length human heat shock protein 90α (Hsp90α), radicicol as the competitor probe ligand, and successful screening of the Selcia fragment library. The CEfrag assay was able to detect weaker affinity (IC(50) >500 µM) fragments than were detected by a fluorescence polarization competition assay using FITC-labeled geldanamycin. The binding site of selected fragments was determined by co-crystallization with recombinant Hsp90α N-terminal domain and X-ray analysis. The results of this study confirm that CEfrag is a sensitive microscale technique enabling detection of fragments binding to the biological target in near-physiological solution.


  • Organizational Affiliation

    Discovery, Selcia Ltd, Fyfield Business and Research Park, Ongar, UK. carol.austin@selcia.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Heat shock protein HSP 90-alpha232Homo sapiensMutation(s): 0 
Gene Names: HSP90AA1HSP90AHSPC1HSPCA
UniProt & NIH Common Fund Data Resources
Find proteins for P07900 (Homo sapiens)
Explore P07900 
Go to UniProtKB:  P07900
PHAROS:  P07900
GTEx:  ENSG00000080824 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP07900
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
RDC
Query on RDC

Download Ideal Coordinates CCD File 
B [auth A]RADICICOL
C18 H17 Cl O6
WYZWZEOGROVVHK-GTMNPGAYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
RDC BindingDB:  4EGK Kd: min: 1.2, max: 46.3 (nM) from 4 assay(s)
IC50: min: 19, max: 200 (nM) from 3 assay(s)
PDBBind:  4EGK Kd: 19 (nM) from 1 assay(s)
Binding MOAD:  4EGK Kd: 19 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.69 Å
  • R-Value Free: 0.243 
  • R-Value Work: 0.201 
  • R-Value Observed: 0.203 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 52.44α = 90
b = 43.88β = 113.81
c = 53.64γ = 90
Software Package:
Software NamePurpose
PROTEUM2data collection
PHASERphasing
REFMACrefinement
PROTEUM2data reduction
PROTEUM2data scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-05-23
    Type: Initial release
  • Version 1.1: 2012-10-17
    Changes: Database references
  • Version 1.2: 2024-02-28
    Changes: Data collection, Database references, Derived calculations