1P2A

The structure of cyclin dependent kinase 2 (CKD2) with a trisubstituted naphthostyril inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.280 
  • R-Value Work: 0.206 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

3,5,6-Trisubstituted Naphthostyrils as CDK2 Inhibitors

Liu, J.-J.Dermatakis, A.Lukacs, C.M.Konzelmann, F.Chen, Y.Kammlott, U.Depinto, W.Yang, H.Yin, X.Chen, Y.Schutt, A.Simcox, M.E.Luk, K.-C.

(2003) Bioorg Med Chem 13: 2465-2468

  • DOI: https://doi.org/10.1016/s0960-894x(03)00488-8
  • Primary Citation of Related Structures:  
    1P2A

  • PubMed Abstract: 

    A novel class of 3,5,6-trisubstituted naphthostyril analogues was designed and synthesized to study the structure-activity relationship for inhibition of cyclin-dependent kinase 2 (CDK2). These compounds, particularly molecules with side-chain modifications providing additional hydrogen bonding capability, were demonstrated to be potent CDK2 inhibitors with cellular activities consistent with CDK2 inhibition. These molecules inhibited tumor cell proliferation and G1-S and G2-M cell-cycle progression in vitro. The X-ray crystal structure of a 2-aminoethyleneamine derivative bound to CDK2, refined to 2.5A resolution, is presented.


  • Organizational Affiliation

    Department of Discovery Chemistry, Hoffmann-La Roche Inc., 340 Kingsland Street, Nutley, NJ 07110, USA. jin-jin.liu@roche.com


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
5BN
Query on 5BN

Download Ideal Coordinates CCD File 
B [auth A]5-[(2-AMINOETHYL)AMINO]-6-FLUORO-3-(1H-PYRROL-2-YL)BENZO[CD]INDOL-2(1H)-ONE
C17 H15 F N4 O
CQCXWWWNUFQYJS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
5BN BindingDB:  1P2A IC50: 12 (nM) from 1 assay(s)
PDBBind:  1P2A IC50: 12 (nM) from 1 assay(s)
Binding MOAD:  1P2A IC50: 12 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.280 
  • R-Value Work: 0.206 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 53.645α = 90
b = 71.406β = 90
c = 71.342γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing
CNXrefinement

Structure Validation

View Full Validation Report



Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2003-07-15
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2024-02-14
    Changes: Data collection, Database references, Derived calculations