2E2B

Crystal structure of the c-Abl kinase domain in complex with INNO-406


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.270 
  • R-Value Work: 0.236 

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This is version 1.3 of the entry. See complete history


Literature

Structural factors contributing to the Abl/Lyn dual inhibitory activity of 3-substituted benzamide derivatives

Horio, T.Hamasaki, T.Inoue, T.Wakayama, T.Itou, S.Naito, H.Asaki, T.Hayase, H.Niwa, T.

(2007) Bioorg Med Chem Lett 17: 2712-2717

  • DOI: https://doi.org/10.1016/j.bmcl.2007.03.002
  • Primary Citation of Related Structures:  
    2E2B

  • PubMed Abstract: 

    To investigate why 3-substituted benzamide derivatives show dual inhibition of Abl and Lyn protein tyrosine kinases, we determined their inhibitory activities against Abl and Lyn, carried out molecular modeling, and conducted a structure-activity relationship study with the aid of a newly determined X-ray structure of the Abl/Lyn dual inhibitor INNO-406 (formerly known as NS-187) bound to human Abl. We found that this series of compounds interacted with both kinases in very similar ways, so that they can inhibit both kinases effectively.


  • Organizational Affiliation

    Research Laboratories, Nippon Shinyaku Co. Ltd., 3-14-1 Sakura, Tsukuba, Ibaraki 305-0003, Japan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Proto-oncogene tyrosine-protein kinase ABL1
A, B
293Homo sapiensMutation(s): 0 
EC: 2.7.10.2
UniProt & NIH Common Fund Data Resources
Find proteins for P00519 (Homo sapiens)
Explore P00519 
Go to UniProtKB:  P00519
PHAROS:  P00519
GTEx:  ENSG00000097007 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00519
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
406
Query on 406

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
N-[3-(4,5'-BIPYRIMIDIN-2-YLAMINO)-4-METHYLPHENYL]-4-{[(3S)-3-(DIMETHYLAMINO)PYRROLIDIN-1-YL]METHYL}-3-(TRIFLUOROMETHYL) BENZAMIDE
C30 H31 F3 N8 O
ZGBAJMQHJDFTQJ-DEOSSOPVSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
406 PDBBind:  2E2B IC50: 11 (nM) from 1 assay(s)
BindingDB:  2E2B IC50: min: 4, max: 26 (nM) from 2 assay(s)
Binding MOAD:  2E2B IC50: 11 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.270 
  • R-Value Work: 0.236 
  • Space Group: F 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 110.82α = 90
b = 147.58β = 90
c = 152.49γ = 90
Software Package:
Software NamePurpose
CNXrefinement
HKL-2000data reduction
HKL-2000data scaling
CNXphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-05-22
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-10-25
    Changes: Data collection, Database references, Derived calculations, Refinement description, Structure summary