2PY3

Crystal Structure of FGF Receptor 2 (FGFR2) Kinase Domain Harboring the Pathogenic E565G Mutation Responsible for Pfeiffer Syndrome


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.252 
  • R-Value Work: 0.217 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.5 of the entry. See complete history


Literature

A molecular brake in the kinase hinge region regulates the activity of receptor tyrosine kinases.

Chen, H.Ma, J.Li, W.Eliseenkova, A.V.Xu, C.Neubert, T.A.Miller, W.T.Mohammadi, M.

(2007) Mol Cell 27: 717-730

  • DOI: https://doi.org/10.1016/j.molcel.2007.06.028
  • Primary Citation of Related Structures:  
    2PSQ, 2PVF, 2PVY, 2PWL, 2PY3, 2PZ5, 2PZP, 2PZR, 2Q0B

  • PubMed Abstract: 

    Activating mutations in the tyrosine kinase domain of receptor tyrosine kinases (RTKs) cause cancer and skeletal disorders. Comparison of the crystal structures of unphosphorylated and phosphorylated wild-type FGFR2 kinase domains with those of seven unphosphorylated pathogenic mutants reveals an autoinhibitory "molecular brake" mediated by a triad of residues in the kinase hinge region of all FGFRs. Structural analysis shows that many other RTKs, including PDGFRs, VEGFRs, KIT, CSF1R, FLT3, TEK, and TIE, are also subject to regulation by this brake. Pathogenic mutations activate FGFRs and other RTKs by disengaging the brake either directly or indirectly.


  • Organizational Affiliation

    Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Fibroblast growth factor receptor 2
A, B
324Homo sapiensMutation(s): 2 
Gene Names: FGFR2BEKKSAM
EC: 2.7.10.1
UniProt & NIH Common Fund Data Resources
Find proteins for P21802 (Homo sapiens)
Explore P21802 
Go to UniProtKB:  P21802
PHAROS:  P21802
GTEx:  ENSG00000066468 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP21802
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ACP
Query on ACP

Download Ideal Coordinates CCD File 
G [auth A],
L [auth B]
PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER
C11 H18 N5 O12 P3
UFZTZBNSLXELAL-IOSLPCCCSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
C [auth A],
D [auth A],
H [auth B],
I [auth B]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
MG
Query on MG

Download Ideal Coordinates CCD File 
E [auth A],
F [auth A],
J [auth B],
K [auth B]
MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.252 
  • R-Value Work: 0.217 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 104.897α = 90
b = 114.748β = 90
c = 64.44γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
AMoREphasing
CNSrefinement
HKL-2000data reduction
HKL-2000data 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: 2007-09-25
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2012-03-07
    Changes: Non-polymer description
  • Version 1.3: 2016-12-21
    Changes: Structure summary
  • Version 1.4: 2021-10-20
    Changes: Database references, Derived calculations
  • Version 1.5: 2023-08-30
    Changes: Data collection, Refinement description