1YC1

Crystal Structures of human HSP90alpha complexed with dihydroxyphenylpyrazoles


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.227 
  • R-Value Work: 0.190 
  • R-Value Observed: 0.190 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Crystal structures of human HSP90alpha-complexed with dihydroxyphenylpyrazoles.

Kreusch, A.Han, S.Brinker, A.Zhou, V.Choi, H.S.He, Y.Lesley, S.A.Caldwell, J.Gu, X.J.

(2005) Bioorg Med Chem Lett 15: 1475-1478

  • DOI: https://doi.org/10.1016/j.bmcl.2004.12.087
  • Primary Citation of Related Structures:  
    1YC1, 1YC3, 1YC4

  • PubMed Abstract: 

    A series of dihydroxyphenylpyrazole compounds were identified as a unique class of reversible Hsp90 inhibitors. The crystal structures for two of the identified compounds complexed with the N-terminal ATP binding domain of human Hsp90alpha were determined. The dihydroxyphenyl ring of the compounds fits deeply into the adenine binding pocket with the C2 hydroxyl group forming a direct hydrogen bond with the side chain of Asp93. The pyrazole ring forms hydrogen bonds to the backbone carbonyl of Gly97, the hydroxyl group of Thr184 and to a water molecule, which is present in all of the published HSP90 structures. One of the identified compounds (G3130) demonstrated cellular activities (in Her-2 degradation and activation of Hsp70 promoter) consistent with the inhibition of cellular Hsp90 functions.


  • Organizational Affiliation

    Genomics Institute of the Novartis Research Foundation (GNF), 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Heat shock protein HSP 90-alpha264Homo sapiensMutation(s): 0 
Gene Names: HSPCAHSP90AHSPC1
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
4BC
Query on 4BC

Download Ideal Coordinates CCD File 
B [auth A]4-(1,3-BENZODIOXOL-5-YL)-5-(5-ETHYL-2,4-DIHYDROXYPHENYL)-2H-PYRAZOLE-3-CARBOXYLIC ACID
C19 H16 N2 O6
LCTWZJKHOGKNMX-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
4BC Binding MOAD:  1YC1 Kd: 680 (nM) from 1 assay(s)
BindingDB:  1YC1 Kd: min: 680, max: 680 (nM) from 2 assay(s)
PDBBind:  1YC1 Kd: 680 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.227 
  • R-Value Work: 0.190 
  • R-Value Observed: 0.190 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 71.611α = 90
b = 89β = 90
c = 88.386γ = 90
Software Package:
Software NamePurpose
CNSrefinement
HKL-2000data reduction
SCALEPACKdata scaling
AMoREphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-02-22
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2024-02-14
    Changes: Data collection, Database references, Derived calculations