1EH4

BINARY COMPLEX OF CASEIN KINASE-1 FROM S. POMBE WITH AN ATP COMPETITIVE INHIBITOR, IC261


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.304 
  • R-Value Work: 0.224 
  • R-Value Observed: 0.224 

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Ligand Structure Quality Assessment 


This is version 1.5 of the entry. See complete history


Literature

Crystal Structure of a Conformation-Selective Casein Kinase-1 Inhibitor

Mashhoon, N.Demaggio, A.J.Tereshko, V.Bergmeier, S.C.Egli, M.Hoekstra, M.F.Kuret, J.

(2000) J Biol Chem 275: 20052-20060

  • DOI: https://doi.org/10.1074/jbc.M001713200
  • Primary Citation of Related Structures:  
    1EH4

  • PubMed Abstract: 

    Members of the casein kinase-1 family of protein kinases play an essential role in cell regulation and disease pathogenesis. Unlike most protein kinases, they appear to function as constitutively active enzymes. As a result, selective pharmacological inhibitors can play an important role in dissection of casein kinase-1-dependent processes. To address this need, new small molecule inhibitors of casein kinase-1 acting through ATP-competitive and ATP-noncompetitive mechanisms were isolated on the basis of in vitro screening. Here we report the crystal structure of 3-[(2,4,6-trimethoxyphenyl) methylidenyl]-indolin-2-one (IC261), an ATP-competitive inhibitor with differential activity among casein kinase-1 isoforms, in complex with the catalytic domain of fission yeast casein kinase-1 refined to a crystallographic R-factor of 22.4% at 2.8 A resolution. The structure reveals that IC261 stabilizes casein kinase-1 in a conformation midway between nucleotide substrate liganded and nonliganded conformations. We propose that adoption of this conformation by casein kinase-1 family members stabilizes a delocalized network of side chain interactions and results in a decreased dissociation rate of inhibitor.


  • Organizational Affiliation

    Center for Biotechnology, Ohio State University College of Medicine, Columbus, Ohio 43210, ICOS Corporation, Bothell, Washington 98021, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CASEIN KINASE-1
A, B
298Schizosaccharomyces pombeMutation(s): 0 
EC: 2.7.1
UniProt
Find proteins for P40233 (Schizosaccharomyces pombe (strain 972 / ATCC 24843))
Explore P40233 
Go to UniProtKB:  P40233
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP40233
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
IC1
Query on IC1

Download Ideal Coordinates CCD File 
I [auth A],
O [auth B]
3-[(2,4,6-TRIMETHOXY-PHENYL)-METHYLENE]-INDOLIN-2-ONE
C18 H17 N O4
JBJYTZXCZDNOJW-JLHYYAGUSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
C [auth A]
D [auth A]
E [auth A]
F [auth A]
G [auth A]
C [auth A],
D [auth A],
E [auth A],
F [auth A],
G [auth A],
H [auth A],
J [auth B],
K [auth B],
L [auth B],
M [auth B],
N [auth B]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.304 
  • R-Value Work: 0.224 
  • R-Value Observed: 0.224 
  • Space Group: P 61
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 113.5α = 90
b = 113.5β = 90
c = 110.4γ = 120
Software Package:
Software NamePurpose
AMoREphasing
CNSrefinement
bioteXdata reduction
bioteXdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2001-09-19
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-10-04
    Changes: Refinement description
  • Version 1.4: 2024-02-07
    Changes: Data collection, Database references, Derived calculations
  • Version 1.5: 2024-03-13
    Changes: Source and taxonomy, Structure summary