4NJ3

Modulating the interaction between CDK2 and Cyclin A with a Quinoline-based inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.231 
  • R-Value Work: 0.182 
  • R-Value Observed: 0.184 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Modulating the interaction between CDK2 and cyclin A with a quinoline-based inhibitor.

Deng, Y.Shipps, G.W.Zhao, L.Siddiqui, M.A.Popovici-Muller, J.Curran, P.J.Duca, J.S.Hruza, A.W.Fischmann, T.O.Madison, V.S.Zhang, R.McNemar, C.W.Mayhood, T.W.Syto, R.Annis, A.Kirschmeier, P.Lees, E.M.Parry, D.A.Windsor, W.T.

(2014) Bioorg Med Chem Lett 24: 199-203

  • DOI: https://doi.org/10.1016/j.bmcl.2013.11.041
  • Primary Citation of Related Structures:  
    4NJ3

  • PubMed Abstract: 

    A new class of quinoline-based kinase inhibitors has been discovered that both disrupt cyclin dependent 2 (CDK2) interaction with its cyclin A subunit and act as ATP competitive inhibitors. The key strategy for discovering this class of protein-protein disrupter compounds was to screen the monomer CDK2 in an affinity-selection/mass spectrometry-based technique and to perform secondary assays that identified compounds that bound only to the inactive CDK2 monomer and not the active CDK2/cyclin A heterodimer. Through a series of chemical modifications the affinity (Kd) of the original hit improved from 1 to 0.005μM.


  • Organizational Affiliation

    Merck Research Laboratories, 320 Bent Street, Cambridge, MA 02141, USA. Electronic address: yongqi.deng@merck.com.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cyclin-dependent kinase 2299Homo sapiensMutation(s): 1 
Gene Names: CDK2CDKN2
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 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
2KD
Query on 2KD

Download Ideal Coordinates CCD File 
B [auth A]6-(3-chlorophenyl)-2-{[(2S)-3-(4-hydroxyphenyl)-1-methoxy-1-oxopropan-2-yl]carbamoyl}quinoline-4-carboxylic acid
C27 H21 Cl N2 O6
LTZGVONWBPMCBP-DEOSSOPVSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
CSD
Query on CSD
A
L-PEPTIDE LINKINGC3 H7 N O4 SCYS
Binding Affinity Annotations 
IDSourceBinding Affinity
2KD BindingDB:  4NJ3 Ki: 140 (nM) from 1 assay(s)
Kd: 300 (nM) from 1 assay(s)
IC50: 1.00e+4 (nM) from 1 assay(s)
PDBBind:  4NJ3 Kd: 300 (nM) from 1 assay(s)
Binding MOAD:  4NJ3 Kd: 300 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.231 
  • R-Value Work: 0.182 
  • R-Value Observed: 0.184 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 53.83α = 90
b = 72.37β = 90
c = 72.42γ = 90
Software Package:
Software NamePurpose
CrystalCleardata collection
BUSTERrefinement
DENZOdata reduction
SCALEPACKdata scaling
BUSTERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-11-27
    Type: Initial release
  • Version 1.1: 2014-01-08
    Changes: Database references