1K3A

Structure of the Insulin-like Growth Factor 1 Receptor Kinase


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.251 
  • R-Value Work: 0.212 
  • R-Value Observed: 0.212 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Structure and autoregulation of the insulin-like growth factor 1 receptor kinase.

Favelyukis, S.Till, J.H.Hubbard, S.R.Miller, W.T.

(2001) Nat Struct Biol 8: 1058-1063

  • DOI: https://doi.org/10.1038/nsb721
  • Primary Citation of Related Structures:  
    1K3A

  • PubMed Abstract: 

    The insulin-like growth factor 1 (IGF1) receptor is closely related to the insulin receptor. However, the unique biological functions of IGF1 receptor make it a target for therapeutic intervention in human cancer. Using its isolated tyrosine kinase domain, we show that the IGF1 receptor is regulated by intermolecular autophosphorylation at three sites within the kinase activation loop. Steady-state kinetic analyses of the isolated phosphorylated forms of the IGF1 receptor kinase (IGF1RK) reveal that each autophosphorylation event increases enzyme turnover number and decreases Km for ATP and peptide. We have determined the 2.1 A-resolution crystal structure of the tris-phosphorylated form of IGF1RK in complex with an ATP analog and a specific peptide substrate. The structure of IGF1RK reveals how the enzyme recognizes peptides containing hydrophobic residues at the P+1 and P+3 positions and how autophosphorylation stabilizes the activation loop in a conformation that facilitates catalysis. Although the nucleotide binding cleft is conserved between IGF1RK and the insulin receptor kinase, sequence differences in the nearby interlobe linker could potentially be exploited for anticancer drug design.


  • Organizational Affiliation

    Department of Physiology and Biophysics, School of Medicine State University of New York at Stony Brook, Stony Brook, New York 11794, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
insulin-like growth factor 1 receptor299Homo sapiensMutation(s): 4 
EC: 2.7.1.112
UniProt & NIH Common Fund Data Resources
Find proteins for P08069 (Homo sapiens)
Explore P08069 
Go to UniProtKB:  P08069
PHAROS:  P08069
GTEx:  ENSG00000140443 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP08069
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
insulin receptor substrate 114N/AMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P35568 (Homo sapiens)
Explore P35568 
Go to UniProtKB:  P35568
PHAROS:  P35568
GTEx:  ENSG00000169047 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP35568
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ACP
Query on ACP

Download Ideal Coordinates CCD File 
C [auth A]PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER
C11 H18 N5 O12 P3
UFZTZBNSLXELAL-IOSLPCCCSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
PTR
Query on PTR
A
L-PEPTIDE LINKINGC9 H12 N O6 PTYR
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.251 
  • R-Value Work: 0.212 
  • R-Value Observed: 0.212 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 80.624α = 90
b = 111.018β = 90
c = 93.297γ = 90
Software Package:
Software NamePurpose
AMoREphasing
CNSrefinement
DENZOdata reduction
SCALEPACKdata 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: 2001-11-28
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-08-16
    Changes: Data collection, Database references, Derived calculations, Refinement description
  • Version 1.4: 2023-11-15
    Changes: Data collection