3MY5

CDk2/cyclinA in complex with DRB


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.219 
  • R-Value Work: 0.180 
  • R-Value Observed: 0.182 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Halogen bonds form the basis for selective P-TEFb inhibition by DRB

Baumli, S.Endicott, J.A.Johnson, L.N.

(2010) Chem Biol 17: 931-936

  • DOI: https://doi.org/10.1016/j.chembiol.2010.07.012
  • Primary Citation of Related Structures:  
    3MY1, 3MY5

  • PubMed Abstract: 

    Cdk9, the kinase of the positive transcription elongation factor b, is required for processive transcription elongation by RNA polymerase II. Cdk9 inhibition contributes to the anticancer activity of many Cdk inhibitors under clinical investigation and hence there is interest in selective Cdk9 inhibitors. DRB (5,6-dichlorobenzimidazone-1-β-D-ribofuranoside) is a commonly used reagent for Cdk9 inhibition in cell biology studies. The crystal structures of Cdk9 and Cdk2 in complex with DRB reported here describe the molecular basis for the DRB selectivity toward Cdk9. The DRB chlorine atoms form halogen bonds that are specific for the Cdk9 kinase hinge region. Kinetic and thermodynamic experiments validate the structural findings and implicate the C-terminal residues of Cdk9 in contributing to the affinity for DRB. These results open the possibility to exploit halogen atoms in inhibitor design to specifically target Cdk9.


  • Organizational Affiliation

    Department of Biochemistry/Laboratory of Molecular Biophysics, University of Oxford, UK. Sonja.baumli@bioch.ox.ac.uk


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cell division protein kinase 2
A, C
300Homo 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
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Cyclin-A2
B, D
262Bos taurusMutation(s): 0 
Gene Names: CCNA2CCNA
UniProt
Find proteins for P30274 (Bos taurus)
Explore P30274 
Go to UniProtKB:  P30274
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP30274
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
TPO
Query on TPO
A, C
L-PEPTIDE LINKINGC4 H10 N O6 PTHR
Binding Affinity Annotations 
IDSourceBinding Affinity
RFZ BindingDB:  3MY5 Ki: 6.50e+4 (nM) from 1 assay(s)
PDBBind:  3MY5 IC50: 6.50e+4 (nM) from 1 assay(s)
Binding MOAD:  3MY5 IC50: 6.50e+4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.219 
  • R-Value Work: 0.180 
  • R-Value Observed: 0.182 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 74.26α = 90
b = 134.26β = 90
c = 148.41γ = 90
Software Package:
Software NamePurpose
ADSCdata collection
PHASERphasing
PHENIXrefinement
MOSFLMdata reduction
SCALAdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-09-29
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-11-01
    Changes: Data collection, Database references, Derived calculations, Refinement description