1E1V

HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR NU2058


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.269 
  • R-Value Work: 0.195 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Identification of Novel Purine and Pyrimidine Cyclin-Dependent Kinase Inhibitors with Distinct Molecular Interactions and Tumor Cell Growth Inhibition Profiles.

Arris, C.E.Boyle, F.T.Calvert, A.H.Curtin, N.J.Endicott, J.A.Garman, E.F.Gibson, A.E.Golding, B.T.Grant, S.Griffin, R.J.Jewsbury, P.Johnson, L.N.Lawrie, A.M.Newell, D.R.Noble, M.E.M.Sausville, E.A.Schultz, R.Yu, W.

(2000) J Med Chem 43: 2797

  • DOI: https://doi.org/10.1021/jm990628o
  • Primary Citation of Related Structures:  
    1E1V, 1E1X

  • PubMed Abstract: 

    Substituted guanines and pyrimidines were tested as inhibitors of cyclin B1/CDK1 and cyclin A3/CDK2 and soaked into crystals of monomeric CDK2. O6-Cyclohexylmethylguanine (NU2058) was a competitive inhibitor of CDK1 and CDK2 with respect to ATP (Ki values: CDK1, 5 +/- 1 microM; CDK2, 12 +/- 3 microM) and formed a triplet of hydrogen bonds (i.e., NH-9 to Glu 81, N-3 to Leu 83, and 2-NH2 to Leu 83). The triplet of hydrogen bonding and CDK inhibition was reproduced by 2,6-diamino-4-cyclohexylmethyloxy-5-nitrosopyrimidine (NU6027, Ki values: CDK1, 2.5 +/- 0.4 microM; CDK2, 1.3 +/- 0.2 microM). Against human tumor cells, NU2058 and NU6027 were growth inhibitory in vitro (mean GI50 values of 13 +/- 7 microM and 10 +/- 6 microM, respectively), with a pattern of sensitivity distinct from flavopiridol and olomoucine. These CDK inhibition and chemosensitivity data indicate that the distinct mode of binding of NU2058 and NU6027 has direct consequences for enzyme and cell growth inhibition.


  • Organizational Affiliation

    Department of Chemistry, University of Newcastle, Newcastle upon Tyne, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CYCLIN-DEPENDENT PROTEIN KINASE 2299Homo 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
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
CMG
Query on CMG

Download Ideal Coordinates CCD File 
B [auth A]6-O-CYCLOHEXYLMETHYL GUANINE
C12 H17 N5 O
MWGXGTJJAOZBNW-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
CMG PDBBind:  1E1V Ki: 1.20e+4 (nM) from 1 assay(s)
Binding MOAD:  1E1V Ki: 1.20e+4 (nM) from 1 assay(s)
BindingDB:  1E1V IC50: 1.70e+4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.269 
  • R-Value Work: 0.195 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 52.62α = 90
b = 71.05β = 90
c = 71.5γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
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: 2001-05-10
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2019-03-06
    Changes: Data collection, Derived calculations, Experimental preparation, Other
  • Version 1.4: 2023-12-06
    Changes: Data collection, Database references, Derived calculations, Refinement description