1CKP

HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR PURVALANOL B


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.05 Å
  • R-Value Free: 0.260 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.192 

Starting Model: experimental
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wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors.

Gray, N.S.Wodicka, L.Thunnissen, A.M.Norman, T.C.Kwon, S.Espinoza, F.H.Morgan, D.O.Barnes, G.LeClerc, S.Meijer, L.Kim, S.H.Lockhart, D.J.Schultz, P.G.

(1998) Science 281: 533-538

  • DOI: https://doi.org/10.1126/science.281.5376.533
  • Primary Citation of Related Structures:  
    1CKP

  • PubMed Abstract: 

    Selective protein kinase inhibitors were developed on the basis of the unexpected binding mode of 2,6,9-trisubstituted purines to the adenosine triphosphate-binding site of the human cyclin-dependent kinase 2 (CDK2). By iterating chemical library synthesis and biological screening, potent inhibitors of the human CDK2-cyclin A kinase complex and of Saccharomyces cerevisiae Cdc28p were identified. The structural basis for the binding affinity and selectivity was determined by analysis of a three-dimensional crystal structure of a CDK2-inhibitor complex. The cellular effects of these compounds were characterized in mammalian cells and yeast. In the latter case the effects were characterized on a genome-wide scale by monitoring changes in messenger RNA levels in treated cells with high-density oligonucleotide probe arrays. Purine libraries could provide useful tools for analyzing a variety of signaling and regulatory pathways and may lead to the development of new therapeutics.


  • Organizational Affiliation

    Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PROTEIN (CYCLIN-DEPENDENT PROTEIN KINASE 2)298Homo sapiensMutation(s): 0 
EC: 2.7.1.37 (PDB Primary Data), 2.7.11.22 (UniProt)
UniProt & NIH Common Fund Data Resources
Find proteins for P24941 (Homo sapiens)
Explore P24941 
Go to UniProtKB:  P24941
PHAROS:  P24941
GTEx:  ENSG00000123374 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP24941
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
PVB
Query on PVB

Download Ideal Coordinates CCD File 
B [auth A]PURVALANOL B
C20 H25 Cl N6 O3
ZKDXRFMOHZVXSG-HNNXBMFYSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
C [auth A]1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
PVB BindingDB:  1CKP IC50: min: 6, max: 9 (nM) from 2 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.05 Å
  • R-Value Free: 0.260 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.192 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 53.55α = 90
b = 71.35β = 90
c = 72γ = 90
Software Package:
Software NamePurpose
CCP4model building
X-PLORrefinement
DENZOdata reduction
SCALEPACKdata scaling
CCP4phasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1999-01-13
    Type: Initial release
  • Version 1.1: 2007-10-16
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-08-09
    Changes: Data collection, Database references, Derived calculations, Refinement description