1W0X

Crystal structure of human CDK2 in complex with the inhibitor olomoucine.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.270 
  • R-Value Work: 0.190 
  • R-Value Observed: 0.190 

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This is version 1.1 of the entry. See complete history


Literature

Multiple Modes of Ligand Recognition: Crystal Structures of Cyclin-Dependent Protein Kinase 2 in Complex with ATP and Two Inhibitors, Olomoucine and Isopentenyladenine.

Schulze-Gahmen, U.Brandsen, J.Jones, H.D.Morgan, D.O.Meijer, L.Vesely, J.Kim, S.H.

(1995) Proteins 22: 378

  • DOI: https://doi.org/10.1002/prot.340220408
  • Primary Citation of Related Structures:  
    1W0X, 2EXM

  • PubMed Abstract: 

    Cyclin-dependent kinases (CDKs) are conserved regulators of the eukaryotic cell cycle with different isoforms controlling specific phases of the cell cycle. Mitogenic or growth inhibitory signals are mediated, respectively, by activation or inhibition of CDKs which phosphorylate proteins associated with the cell cycle. The central role of CDKs in cell cycle regulation makes them a potential new target for inhibitory molecules with anti-proliferative and/or anti-neoplastic effects. We describe the crystal structures of the complexes of CDK2 with a weakly specific CDK inhibitor, N6-(delta 2-isopentenyl)adenine, and a strongly specific inhibitor, olomoucine. Both inhibitors are adenine derivatives and bind in the adenine binding pocket of CDK2, but in an unexpected and different orientation from the adenine of the authentic ligand ATP. The N6-benzyl substituent in olomoucine binds outside the conserved binding pocket and is most likely responsible for its specificity. The structural information from the CDK2-olomoucine complex will be useful in directing the search for the next generation inhibitors with improved properties.


  • Organizational Affiliation

    Department of Chemistry, University of California, Berkeley 94720, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CYCLIN-DEPENDENT KINASE 2A [auth C]298Homo sapiensMutation(s): 0 
EC: 2.7.1.37
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 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
OLO
Query on OLO

Download Ideal Coordinates CCD File 
B [auth C]OLOMOUCINE
C15 H18 N6 O
GTVPOLSIJWJJNY-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
OLO BindingDB:  1W0X IC50: min: 7, max: 1.00e+4 (nM) from 6 assay(s)
PDBBind:  1W0X IC50: 5000 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.270 
  • R-Value Work: 0.190 
  • R-Value Observed: 0.190 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 73.77α = 90
b = 72.55β = 90
c = 54.06γ = 90
Software Package:
Software NamePurpose
X-PLORrefinement

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-01-14
    Type: Initial release
  • Version 1.1: 2014-02-05
    Changes: Database references, Derived calculations, Non-polymer description, Other, Source and taxonomy, Structure summary, Version format compliance