1M17

Epidermal Growth Factor Receptor tyrosine kinase domain with 4-anilinoquinazoline inhibitor erlotinib


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.295 
  • R-Value Work: 0.251 
  • R-Value Observed: 0.251 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor.

Stamos, J.Sliwkowski, M.X.Eigenbrot, C.

(2002) J Biol Chem 277: 46265-46272

  • DOI: https://doi.org/10.1074/jbc.M207135200
  • Primary Citation of Related Structures:  
    1M14, 1M17

  • PubMed Abstract: 

    The crystal structure of the kinase domain from the epidermal growth factor receptor (EGFRK) including forty amino acids from the carboxyl-terminal tail has been determined to 2.6-A resolution, both with and without an EGFRK-specific inhibitor currently in Phase III clinical trials as an anti-cancer agent, erlotinib (OSI-774, CP-358,774, Tarceva(TM)). The EGFR family members are distinguished from all other known receptor tyrosine kinases in possessing constitutive kinase activity without a phosphorylation event within their kinase domains. Despite its lack of phosphorylation, we find that the EGFRK activation loop adopts a conformation similar to that of the phosphorylated active form of the kinase domain from the insulin receptor. Surprisingly, key residues of a putative dimerization motif lying between the EGFRK domain and carboxyl-terminal substrate docking sites are found in close contact with the kinase domain. Significant intermolecular contacts involving the carboxyl-terminal tail are discussed with respect to receptor oligomerization.


  • Organizational Affiliation

    Department of Protein Engineering, Genentech, Inc., South San Francisco, California 94080, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
epidermal growth factor receptor333Homo sapiensMutation(s): 0 
Gene Names: egfr
EC: 2.7.1.112
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
AQ4
Query on AQ4

Download Ideal Coordinates CCD File 
B [auth A][6,7-BIS(2-METHOXY-ETHOXY)QUINAZOLINE-4-YL]-(3-ETHYNYLPHENYL)AMINE
C22 H23 N3 O4
AAKJLRGGTJKAMG-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
AQ4 BindingDB:  1M17 Ki: min: 0.1, max: 136 (nM) from 6 assay(s)
Kd: min: 0.35, max: 970 (nM) from 15 assay(s)
IC50: min: 0.03, max: 260 (nM) from 53 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.295 
  • R-Value Work: 0.251 
  • R-Value Observed: 0.251 
  • Space Group: I 2 3
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 147.8α = 90
b = 147.8β = 90
c = 147.8γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
TRUNCATEdata reduction
AMoREphasing
X-PLORrefinement
CCP4data 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: 2002-09-04
    Type: Initial release
  • Version 1.1: 2008-04-28
    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, Refinement description