5IH4

Human Casein Kinase 1 isoform delta apo (kinase domain)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.227 
  • R-Value Work: 0.191 
  • R-Value Observed: 0.193 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Epiblastin A Induces Reprogramming of Epiblast Stem Cells Into Embryonic Stem Cells by Inhibition of Casein Kinase 1.

Ursu, A.Illich, D.J.Takemoto, Y.Porfetye, A.T.Zhang, M.Brockmeyer, A.Janning, P.Watanabe, N.Osada, H.Vetter, I.R.Ziegler, S.Scholer, H.R.Waldmann, H.

(2016) Cell Chem Biol 23: 494-507

  • DOI: https://doi.org/10.1016/j.chembiol.2016.02.015
  • Primary Citation of Related Structures:  
    5IH4, 5IH5, 5IH6

  • PubMed Abstract: 

    The discovery of novel small molecules that induce stem cell reprogramming and give efficient access to pluripotent stem cells is of major importance for potential therapeutic applications and may reveal novel insights into the factors controlling pluripotency. Chemical reprogramming of mouse epiblast stem cells (EpiSCs) into cells corresponding to embryonic stem cells (cESCs) is an inefficient process. In order to identify small molecules that promote this cellular transition, we analyzed the LOPAC library in a phenotypic screen monitoring Oct4-GFP expression and identified triamterene (TR) as initial hit. Synthesis of a TR-derived compound collection and investigation for reprogramming of EpiSCs into cESCs identified casein kinases 1 (CK1) α/δ/ɛ as responsible cellular targets of TR and unraveled the structural parameters that determine reprogramming. Delineation of a structure-activity relationship led to the development of Epiblastin A, which engages CK1 isoenzymes in cell lysate and induces efficient conversion of EpiSCs into cESCs.


  • Organizational Affiliation

    Department of Chemical Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany; Chemical Biology, Faculty of Chemistry and Chemical Biology, Technical University Dortmund, Otto-Hahn-Strasse 6, 44221 Dortmund, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Casein kinase I isoform delta294Homo sapiensMutation(s): 0 
Gene Names: CSNK1DHCKID
EC: 2.7.11.1 (PDB Primary Data), 2.7.11.26 (PDB Primary Data)
UniProt & NIH Common Fund Data Resources
Find proteins for P48730 (Homo sapiens)
Explore P48730 
Go to UniProtKB:  P48730
PHAROS:  P48730
GTEx:  ENSG00000141551 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP48730
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.227 
  • R-Value Work: 0.191 
  • R-Value Observed: 0.193 
  • Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 64.999α = 90
b = 64.999β = 90
c = 152.881γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2016-04-13
    Type: Initial release
  • Version 1.1: 2016-04-20
    Changes: Database references
  • Version 1.2: 2016-05-04
    Changes: Database references
  • Version 1.3: 2024-01-10
    Changes: Data collection, Database references, Derived calculations, Refinement description