1AGW

CRYSTAL STRUCTURE OF THE TYROSINE KINASE DOMAIN OF FIBROBLAST GROWTH FACTOR RECEPTOR 1 IN COMPLEX WITH SU4984 INHIBITOR


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.280 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.194 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Structures of the tyrosine kinase domain of fibroblast growth factor receptor in complex with inhibitors.

Mohammadi, M.McMahon, G.Sun, L.Tang, C.Hirth, P.Yeh, B.K.Hubbard, S.R.Schlessinger, J.

(1997) Science 276: 955-960

  • DOI: https://doi.org/10.1126/science.276.5314.955
  • Primary Citation of Related Structures:  
    1AGW, 1FGI

  • PubMed Abstract: 

    A new class of protein tyrosine kinase inhibitors was identified that is based on an oxindole core (indolinones). Two compounds from this class inhibited the kinase activity of fibroblast growth factor receptor 1 (FGFR1) and showed differential specificity toward other receptor tyrosine kinases. Crystal structures of the tyrosine kinase domain of FGFR1 in complex with the two compounds were determined. The oxindole occupies the site in which the adenine of adenosine triphosphate binds, whereas the moieties that extend from the oxindole contact residues in the hinge region between the two kinase lobes. The more specific inhibitor of FGFR1 induces a conformational change in the nucleotide-binding loop. This structural information will facilitate the design of new inhibitors for use in the treatment of cancer and other diseases in which cell signaling by tyrosine kinases plays a crucial role in disease pathogenesis.


  • Organizational Affiliation

    Department of Pharmacology, New York University Medical Center, New York, NY 10016, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
FGF RECEPTOR 1
A, B
310Homo sapiensMutation(s): 1 
EC: 2.7.1.112
UniProt & NIH Common Fund Data Resources
Find proteins for P11362 (Homo sapiens)
Explore P11362 
Go to UniProtKB:  P11362
PHAROS:  P11362
GTEx:  ENSG00000077782 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP11362
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SU2
Query on SU2

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
3-[4-(1-FORMYLPIPERAZIN-4-YL)-BENZYLIDENYL]-2-INDOLINONE
C20 H21 N3 O2
AZGZGRJOCKSSHA-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
SU2 PDBBind:  1AGW IC50: 2.00e+4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.280 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.194 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 208.36α = 90
b = 57.08β = 107.54
c = 65.53γ = 90
Software Package:
Software NamePurpose
X-PLORmodel building
X-PLORrefinement
DENZOdata reduction
SCALEPACKdata scaling
X-PLORphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1998-03-25
    Type: Initial release
  • Version 1.1: 2008-03-24
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2021-11-03
    Changes: Database references, Derived calculations, Other
  • Version 1.4: 2024-02-07
    Changes: Data collection