4F9B

Human CDC7 kinase in complex with DBF4 and PHA767491


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.239 
  • R-Value Work: 0.187 
  • R-Value Observed: 0.190 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Crystal structure of human CDC7 kinase in complex with its activator DBF4.

Hughes, S.Elustondo, F.Di Fonzo, A.Leroux, F.G.Wong, A.C.Snijders, A.P.Matthews, S.J.Cherepanov, P.

(2012) Nat Struct Mol Biol 19: 1101-1107

  • DOI: https://doi.org/10.1038/nsmb.2404
  • Primary Citation of Related Structures:  
    4F99, 4F9A, 4F9B, 4F9C

  • PubMed Abstract: 

    CDC7 is a serine/threonine kinase that is essential for the initiation of eukaryotic DNA replication. CDC7 activity is controlled by its activator, DBF4. Here we present crystal structures of human CDC7-DBF4 in complex with a nucleotide or ATP-competing small molecules, revealing the active and inhibited forms of the kinase, respectively. DBF4 wraps around CDC7, burying approximately 6,000 Å(2) of hydrophobic molecular surface in a bipartite interface. The effector domain of DBF4, containing conserved motif C, is essential and sufficient to support CDC7 kinase activity by binding to the kinase N-terminal lobe and stabilizing its canonical αC helix. DBF4 motif M latches onto the C-terminal lobe of the kinase, acting as a tethering domain. Our results elucidate the structural basis for binding to and activation of CDC7 by DBF4 and provide a framework for the design of more potent and specific CDC7 inhibitors.


  • Organizational Affiliation

    Cancer Research UK, London Research Institute, Clare Hall Laboratories, Potters Bar, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cell division cycle 7-related protein kinase
A, C
361Homo sapiensMutation(s): 0 
Gene Names: CDC7CDC7L1
EC: 2.7.11.1
UniProt & NIH Common Fund Data Resources
Find proteins for O00311 (Homo sapiens)
Explore O00311 
Go to UniProtKB:  O00311
PHAROS:  O00311
GTEx:  ENSG00000097046 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO00311
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Protein DBF4 homolog A
B, D
144Homo sapiensMutation(s): 0 
Gene Names: ASKDBF4DBF4AZDBF1
UniProt & NIH Common Fund Data Resources
Find proteins for Q9UBU7 (Homo sapiens)
Explore Q9UBU7 
Go to UniProtKB:  Q9UBU7
PHAROS:  Q9UBU7
GTEx:  ENSG00000006634 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9UBU7
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
0SY BindingDB:  4F9B IC50: min: 1, max: 10 (nM) from 3 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.239 
  • R-Value Work: 0.187 
  • R-Value Observed: 0.190 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 60.92α = 90
b = 67.88β = 90
c = 238.16γ = 90
Software Package:
Software NamePurpose
ADSCdata collection
REFMACrefinement
XDSdata reduction
SCALAdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-10-31
    Type: Initial release
  • Version 1.1: 2012-12-12
    Changes: Database references
  • Version 1.2: 2017-08-16
    Changes: Source and taxonomy
  • Version 1.3: 2017-11-15
    Changes: Refinement description
  • Version 1.4: 2024-02-28
    Changes: Data collection, Database references, Derived calculations