3LOK

Drug resistant cSrc kinase domain in complex with covalent inhibitor PD168393


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.48 Å
  • R-Value Free: 0.286 
  • R-Value Work: 0.221 
  • R-Value Observed: 0.225 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Characterization of irreversible kinase inhibitors by directly detecting covalent bond formation: a tool for dissecting kinase drug resistance

Klueter, S.Simard, J.R.Rode, H.B.Gruetter, C.Pawar, V.Raaijmakers, H.C.Barf, T.A.Rabiller, M.van Otterlo, W.A.L.Rauh, D.

(2010) Chembiochem 11: 2557-2566

  • DOI: https://doi.org/10.1002/cbic.201000352
  • Primary Citation of Related Structures:  
    3LOK

  • PubMed Abstract: 

    Targeting protein kinases in cancer therapy with irreversible small-molecule inhibitors is moving to the forefront of kinase-inhibitor research and is thought to be an effective means of overcoming mutation-associated drug resistance in epidermal growth factor receptor kinase (EGFR). We generated a detection technique that allows direct measurements of covalent bond formation without relying on kinase activity, thereby allowing the straightforward investigation of the influence of steric clashes on covalent inhibitors in different resistant kinase mutants. The obtained results are discussed together with structural biology and biochemical studies of catalytic activity in both wild-type and gatekeeper mutated kinase variants to draw conclusions about the impact of steric hindrance and increased catalytic activity in drug-resistant kinase variants.


  • Organizational Affiliation

    Chemical Genomics Centre of the Max Planck Society, Otto-Hahn-Strasse 15, 44227 Dortmund, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Proto-oncogene tyrosine-protein kinase Src
A, B
286Gallus gallusMutation(s): 2 
Gene Names: SRCv-Src sarcoma viral oncogene
EC: 2.7.10.2
UniProt
Find proteins for P00523 (Gallus gallus)
Explore P00523 
Go to UniProtKB:  P00523
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00523
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
DJK
Query on DJK

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
N-[4-(3-BROMO-PHENYLAMINO)-QUINAZOLIN-6-YL]-ACRYLAMIDE
C17 H13 Br N4 O
HTUBKQUPEREOGA-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
DJK PDBBind:  3LOK IC50: 120 (nM) from 1 assay(s)
BindingDB:  3LOK IC50: min: 340, max: 2.70e+4 (nM) from 4 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.48 Å
  • R-Value Free: 0.286 
  • R-Value Work: 0.221 
  • R-Value Observed: 0.225 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.09α = 78.49
b = 63.26β = 88.33
c = 74.22γ = 90
Software Package:
Software NamePurpose
MOSFLMdata reduction
SCALAdata scaling
PHASERphasing
REFMACrefinement
PDB_EXTRACTdata extraction
MAR345dtbdata collection

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-12-22
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-11-01
    Changes: Data collection, Database references, Derived calculations, Refinement description