1G5S

CRYSTAL STRUCTURE OF HUMAN CYCLIN DEPENDENT KINASE 2 (CDK2) IN COMPLEX WITH THE INHIBITOR H717


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.61 Å
  • R-Value Free: 0.242 
  • R-Value Work: 0.201 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Crystal structure of human cyclin-dependent kinase 2 in complex with the adenine-derived inhibitor H717.

Dreyer, M.K.Borcherding, D.R.Dumont, J.A.Peet, N.P.Tsay, J.T.Wright, P.S.Bitonti, A.J.Shen, J.Kim, S.H.

(2001) J Med Chem 44: 524-530

  • DOI: https://doi.org/10.1021/jm001043t
  • Primary Citation of Related Structures:  
    1G5S

  • PubMed Abstract: 

    Cyclin-dependent kinases (CDKs) are regulatory proteins of the eukaryotic cell cycle. They act after association with different cyclins, the concentrations of which vary throughout the progression of the cell cycle. As central mediators of cell growth, CDKs are potential targets for inhibitory molecules that would allow disruption of the cell cycle in order to evoke an antiproliferative effect and may therefore be useful as cancer therapeutics. We synthesized several inhibitory 2,6,9-trisubstituted purine derivatives and solved the crystal structure of one of these compounds, H717, in complex with human CDK2 at 2.6 A resolution. The orientation of the C2-p-diaminocyclohexyl portion of the inhibitor is strikingly different from those of similar moieties in other related inhibitor complexes. The N9-cyclopentyl ring fully occupies a space in the enzyme which is otherwise empty, while the C6-N-aminobenzyl substituent points out of the ATP-binding site. The structure provides a basis for the further development of more potent inhibitory drugs.


  • Organizational Affiliation

    Department of Chemistry and Lawrence Berkeley National Laboratory, University of California, Berkeley, California 94720, USA. dreyer@biozentrum.uni.wuerzburg.de


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CELL DIVISION PROTEIN KINASE 2298Homo sapiensMutation(s): 0 
Gene Names: CDK2
EC: 2.7.1
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
I17
Query on I17

Download Ideal Coordinates CCD File 
B [auth A]2-[TRANS-(4-AMINOCYCLOHEXYL)AMINO]-6-(BENZYL-AMINO)-9-CYCLOPENTYLPURINE
C23 H31 N7
JTVILUUAQWQWBK-IYARVYRRSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
I17 PDBBind:  1G5S IC50: 48 (nM) from 1 assay(s)
BindingDB:  1G5S IC50: 48 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.61 Å
  • R-Value Free: 0.242 
  • R-Value Work: 0.201 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 54.18α = 90
b = 72.84β = 90
c = 73.47γ = 90
Software Package:
Software NamePurpose
X-PLORmodel building
CNSrefinement
SCALEPACKdata scaling
X-PLORphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2001-11-02
    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: 2018-04-04
    Changes: Data collection
  • Version 1.5: 2023-08-09
    Changes: Data collection, Database references, Derived calculations, Refinement description