5H22

Hsp90 alpha N-terminal domain in complex with an inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.208 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.195 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Synthesis and in vitro antiproliferative activity of C5-benzyl substituted 2-amino-pyrrolo[2,3-d]pyrimidines as potent Hsp90 inhibitors.

Lee, J.H.Shin, S.C.Seo, S.H.Seo, Y.H.Jeong, N.Kim, C.W.Kim, E.E.Keum, G.

(2017) Bioorg Med Chem Lett 27: 237-241

  • DOI: https://doi.org/10.1016/j.bmcl.2016.11.062
  • Primary Citation of Related Structures:  
    5H22

  • PubMed Abstract: 

    A novel series of heat shock protein 90 (Hsp90) inhibitors was identified by X-ray crystal analysis of complex structures at solvent-exposed exit pocket C. The 2-amino-pyrrolo[2,3-d]pyrimidine derivatives, 7-deazapurines substituted with a benzyl moiety at C5, showed potent Hsp90 inhibition and broad-spectrum antiproliferative activity against NCI-60 cancer cell lines. The most potent compound, 6a, inhibited Hsp90 with an IC 50 of 36nM and showed a submicromolar mean GI 50 value against NCI-60 cell lines. The interaction of 6a at the ATP-binding pocket of Hsp90 was confirmed by X-ray crystallography and Western blot analysis.


  • Organizational Affiliation

    Center for Neuro-Medicine, Korea Institute of Science and Technology (KIST), Hwarangro 14-gil 5, Seongbuk-gu, Seoul 02792, Republic of Korea; Department of Chemistry, Korea University, Anam-ro 145, Seongbuk-gu, Seoul 02841, Republic of Korea.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Hsp90aa1 protein215Mus musculusMutation(s): 0 
Gene Names: Hsp90aa1
UniProt & NIH Common Fund Data Resources
Find proteins for P07901 (Mus musculus)
Explore P07901 
Go to UniProtKB:  P07901
IMPC:  MGI:96250
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP07901
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
7FT
Query on 7FT

Download Ideal Coordinates CCD File 
B [auth A]4-chloranyl-7-[(4-methoxy-3,5-dimethyl-pyridin-2-yl)methyl]-5-(phenylmethyl)pyrrolo[2,3-d]pyrimidin-2-amine
C22 H22 Cl N5 O
CBDCNHPEKJZUHT-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
7FT BindingDB:  5H22 IC50: 36 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.208 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.195 
  • Space Group: I 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 66.787α = 90
b = 90.581β = 90
c = 98.943γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
PDB_EXTRACTdata extraction
HKL-2000data processing
HKL-2000data scaling
MOLREPphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Korea, Republic OfNRF 20110021713

Revision History  (Full details and data files)

  • Version 1.0: 2017-10-11
    Type: Initial release
  • Version 1.1: 2019-04-24
    Changes: Data collection, Database references
  • Version 1.2: 2023-11-08
    Changes: Data collection, Database references, Refinement description