3D0B

Crystal Structure of Benzamide Tetrahydro-4H-carbazol-4-one bound to Hsp90


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.74 Å
  • R-Value Free: 0.228 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.202 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Discovery of benzamide tetrahydro-4H-carbazol-4-ones as novel small molecule inhibitors of Hsp90

Barta, T.E.Veal, J.M.Rice, J.W.Partridge, J.M.Fadden, R.P.Ma, W.Jenks, M.Geng, L.Hanson, G.J.Huang, K.H.Barabasz, A.F.Foley, B.E.Otto, J.Hall, S.E.

(2008) Bioorg Med Chem Lett 18: 3517-3521

  • DOI: https://doi.org/10.1016/j.bmcl.2008.05.023
  • Primary Citation of Related Structures:  
    3D0B

  • PubMed Abstract: 

    Hsp90 maintains the conformational stability of multiple proteins implicated in oncogenesis and has emerged as a target for chemotherapy. We report here the discovery of a novel small molecule scaffold that inhibits Hsp90. X-ray data show that the scaffold binds competitively at the ATP site on Hsp90. Cellular proliferation and client assays demonstrate that members of the series are able to inhibit Hsp90 at nanomolar concentrations.


  • Organizational Affiliation

    Serenex, Inc., 323 Foster St., Durham, NC 27701, USA.


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 
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
SNX
Query on SNX

Download Ideal Coordinates CCD File 
B [auth A]2-[(2-methoxyethyl)amino]-4-(4-oxo-1,2,3,4-tetrahydro-9H-carbazol-9-yl)benzamide
C22 H23 N3 O3
XQKFKSJUBJPOLY-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
SNX Binding MOAD:  3D0B Kd: 290 (nM) from 1 assay(s)
PDBBind:  3D0B Kd: 290 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.74 Å
  • R-Value Free: 0.228 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.202 
  • Space Group: I 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 66.853α = 90
b = 90.595β = 90
c = 98.215γ = 90
Software Package:
Software NamePurpose
REFMACrefinement

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-06-17
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2024-02-21
    Changes: Data collection, Database references, Derived calculations