5J9Z

EGFR-T790M in complex with pyrazolopyrimidine inhibitor 1a


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.239 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.198 

Starting Model: experimental
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wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Insight into the Inhibition of Drug-Resistant Mutants of the Receptor Tyrosine Kinase EGFR.

Engel, J.Becker, C.Lategahn, J.Keul, M.Ketzer, J.Muhlenberg, T.Kollipara, L.Schultz-Fademrecht, C.Zahedi, R.P.Bauer, S.Rauh, D.

(2016) Angew Chem Int Ed Engl 55: 10909-10912

  • DOI: https://doi.org/10.1002/anie.201605011
  • Primary Citation of Related Structures:  
    5J9Y, 5J9Z

  • PubMed Abstract: 

    Targeting acquired drug resistance represents the major challenge in the treatment of EGFR-driven non-small-cell lung cancer (NSCLC). Herein, we describe the structure-based design, synthesis, and biological evaluation of a novel class of covalent EGFR inhibitors that exhibit excellent inhibition of EGFR-mutant drug-resistant cells. Protein X-ray crystallography combined with detailed kinetic studies led to a deeper understanding of the mode of inhibition of EGFR-T790M and provided insight into the key principles for effective inhibition of the recently discovered tertiary mutation at EGFR-C797S.


  • Organizational Affiliation

    Technische Universität Dortmund, Fakultät für Chemie und Chemische Biologie, Otto-Hahn-Strasse 4a, 44227, Dortmund, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Epidermal growth factor receptor325Homo sapiensMutation(s): 1 
Gene Names: EGFRERBBERBB1HER1
EC: 2.7.10.1
UniProt & NIH Common Fund Data Resources
Find proteins for P00533 (Homo sapiens)
Explore P00533 
Go to UniProtKB:  P00533
PHAROS:  P00533
GTEx:  ENSG00000146648 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00533
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
6HJ
Query on 6HJ

Download Ideal Coordinates CCD File 
B [auth A](R)-1-(3-(4-amino-3-(1-methyl-1H-indol-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one
C22 H23 N7 O
KFYRXHYWURCCBT-CQSZACIVSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.239 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.198 
  • Space Group: I 2 3
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 146.46α = 90
b = 146.46β = 90
c = 146.46γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
XSCALEdata scaling
PDB_EXTRACTdata extraction
XDSdata reduction
PHASERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2016-08-17
    Type: Initial release
  • Version 1.1: 2016-09-07
    Changes: Database references
  • Version 1.2: 2019-02-20
    Changes: Advisory, Data collection, Derived calculations
  • Version 1.3: 2024-01-10
    Changes: Data collection, Database references, Refinement description
  • Version 1.4: 2024-10-23
    Changes: Structure summary