1OPK

Structural basis for the auto-inhibition of c-Abl tyrosine kinase


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.221 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.196 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Structural basis for the autoinhibition of c-Abl tyrosine kinase

Nagar, B.Hantschel, O.Young, M.A.Scheffzek, K.Veach, D.Bornmann, W.Clarkson, B.Superti-Furga, G.Kuriyan, J.

(2003) Cell 112: 859-871

  • DOI: https://doi.org/10.1016/s0092-8674(03)00194-6
  • Primary Citation of Related Structures:  
    1OPJ, 1OPK, 1OPL

  • PubMed Abstract: 

    c-Abl is normally regulated by an autoinhibitory mechanism, the disruption of which leads to chronic myelogenous leukemia. The details of this mechanism have been elusive because c-Abl lacks a phosphotyrosine residue that triggers the assembly of the autoinhibited form of the closely related Src kinases by internally engaging the SH2 domain. Crystal structures of c-Abl show that the N-terminal myristoyl modification of c-Abl 1b binds to the kinase domain and induces conformational changes that allow the SH2 and SH3 domains to dock onto it. Autoinhibited c-Abl forms an assembly that is strikingly similar to that of inactive Src kinases but with specific differences that explain the differential ability of the drug STI-571/Gleevec/imatinib (STI-571) to inhibit the catalytic activity of Abl, but not that of c-Src.


  • Organizational Affiliation

    Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Proto-oncogene tyrosine-protein kinase ABL1495Mus musculusMutation(s): 1 
Gene Names: ABL1
EC: 2.7.1.112
UniProt
Find proteins for P00520 (Mus musculus)
Explore P00520 
Go to UniProtKB:  P00520
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00520
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
P16
Query on P16

Download Ideal Coordinates CCD File 
C [auth A]6-(2,6-DICHLOROPHENYL)-2-{[3-(HYDROXYMETHYL)PHENYL]AMINO}-8-METHYLPYRIDO[2,3-D]PYRIMIDIN-7(8H)-ONE
C21 H16 Cl2 N4 O2
ZIQFYVPVJZEOFS-UHFFFAOYSA-N
MYR
Query on MYR

Download Ideal Coordinates CCD File 
B [auth A]MYRISTIC ACID
C14 H28 O2
TUNFSRHWOTWDNC-UHFFFAOYSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
D [auth A]GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
P16 BindingDB:  1OPK IC50: 2.8 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.221 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.196 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 118.328α = 90
b = 123.943β = 90
c = 74.798γ = 90
Software Package:
Software NamePurpose
CNSrefinement
HKL-2000data reduction
SCALEPACKdata scaling
AMoREphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2003-04-08
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.3: 2021-10-27
    Changes: Database references, Derived calculations
  • Version 1.4: 2023-08-16
    Changes: Data collection, Refinement description