RCSB PDB - 4YBK: C-Helix-Out Dasatinib Analog Crystallized with c-Src Kinase

 4YBK

C-Helix-Out Dasatinib Analog Crystallized with c-Src Kinase


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.252 
  • R-Value Work: 0.206 
  • R-Value Observed: 0.208 

Starting Model: experimental
View more details

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted 4B7Click on this verticalbar to view details

This is version 1.2 of the entry. See complete history


Literature

Conformation-Selective Analogues of Dasatinib Reveal Insight into Kinase Inhibitor Binding and Selectivity.

Kwarcinski, F.E.Brandvold, K.R.Phadke, S.Beleh, O.M.Johnson, T.K.Meagher, J.L.Seeliger, M.A.Stuckey, J.A.Soellner, M.B.

(2016) ACS Chem Biol 11: 1296-1304

  • DOI: https://doi.org/10.1021/acschembio.5b01018
  • Primary Citation of Related Structures:  
    4YBJ, 4YBK, 4YC8

  • PubMed Abstract: 

    In the kinase field, there are many widely held tenets about conformation-selective inhibitors that have yet to be validated using controlled experiments. We have designed, synthesized, and characterized a series of kinase inhibitor analogues of dasatinib, an FDA-approved kinase inhibitor that binds the active conformation. This inhibitor series includes two Type II inhibitors that bind the DFG-out inactive conformation and two inhibitors that bind the αC-helix-out inactive conformation. Using this series of compounds, we analyze the impact that conformation-selective inhibitors have on target binding and kinome-wide selectivity.


  • Organizational Affiliation

    Department of Pharmacological Sciences, Stony Brook University , Stony Brook, New York 11794, United States.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Proto-oncogene tyrosine-protein kinase Src286Gallus gallusMutation(s): 0 
Gene Names: SRC
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
4B7
Query on 4B7

Download Ideal Coordinates CCD File 
B [auth A]2-({6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl}amino)-N-(4-phenoxyphenyl)-1,3-thiazole-5-carboxamide
C27 H29 N7 O3 S
QUFCHHSHOLSVOT-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
4B7 BindingDB:  4YBK Kd: 15 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.252 
  • R-Value Work: 0.206 
  • R-Value Observed: 0.208 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 41.334α = 90
b = 62.213β = 90
c = 102.803γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
HKL-2000data scaling
BUSTER-TNTrefinement
PDB_EXTRACTdata extraction
PHASERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted 4B7Click on this verticalbar to view details

Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2016-03-02
    Type: Initial release
  • Version 1.1: 2016-06-01
    Changes: Database references
  • Version 1.2: 2023-09-27
    Changes: Data collection, Database references, Derived calculations, Refinement description