3TIY

CDK2 in complex with NSC 35676


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.84 Å
  • R-Value Free: 0.224 
  • R-Value Work: 0.184 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

A Novel Approach to the Discovery of Small-Molecule Ligands of CDK2.

Martin, M.P.Alam, R.Betzi, S.Ingles, D.J.Zhu, J.Y.Schonbrunn, E.

(2012) Chembiochem 13: 2128-2136

  • DOI: https://doi.org/10.1002/cbic.201200316
  • Primary Citation of Related Structures:  
    3TI1, 3TIY, 3TIZ, 4ERW, 4EZ3, 4EZ7

  • PubMed Abstract: 

    In an attempt to identify novel small-molecule ligands of cyclin-dependent kinase 2 (CDK2) with potential as allosteric inhibitors, we have devised a robust and cost-effective fluorescence-based high-throughput screening assay. The assay is based on the specific interaction of CDK2 with the extrinsic fluorophore 8-anilino-1-naphthalene sulfonate (ANS), which binds to a large allosteric pocket adjacent to the ATP site. Hit compounds that displace ANS directly or indirectly from CDK2 are readily classified as ATP site binders or allosteric ligands through the use of staurosporine, which blocks the ATP site without displacing ANS. Pilot screening of 1453 compounds led to the discovery of 12 compounds with displacement activities (EC(50) values) ranging from 6 to 44 μM, all of which were classified as ATP-site-directed ligands. Four new type I inhibitor scaffolds were confirmed by X-ray crystallography. Although this small compound library contained only ATP-site-directed ligands, the application of this assay to large compound libraries has the potential to reveal previously unrecognized chemical scaffolds suitable for structure-based design of CDK2 inhibitors with new mechanisms of action.


  • Organizational Affiliation

    Drug Discovery Department, Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cyclin-dependent kinase 2298Homo sapiensMutation(s): 0 
Gene Names: CDK2
EC: 2.7.11.22
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 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
TIY
Query on TIY

Download Ideal Coordinates CCD File 
N [auth A]2,3,4,6-tetrahydroxy-5H-benzo[7]annulen-5-one
C11 H8 O5
WDGFFVCWBZVLCE-UHFFFAOYSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
B [auth A]
C [auth A]
D [auth A]
E [auth A]
F [auth A]
B [auth A],
C [auth A],
D [auth A],
E [auth A],
F [auth A],
G [auth A],
H [auth A],
I [auth A],
J [auth A],
K [auth A],
L [auth A],
M [auth A]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
TIY PDBBind:  3TIY IC50: 1.70e+4 (nM) from 1 assay(s)
BindingDB:  3TIY IC50: 1.70e+4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.84 Å
  • R-Value Free: 0.224 
  • R-Value Work: 0.184 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 53.47α = 90
b = 71.99β = 90
c = 72.31γ = 90
Software Package:
Software NamePurpose
PHENIXmodel building
PHENIXrefinement
XDSdata reduction
XDSdata scaling
PHENIXphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-08-22
    Type: Initial release
  • Version 1.1: 2012-08-29
    Changes: Database references
  • Version 1.2: 2012-10-10
    Changes: Database references
  • Version 1.3: 2013-07-17
    Changes: Non-polymer description
  • Version 1.4: 2024-02-28
    Changes: Data collection, Database references, Derived calculations