3IPX

X-Ray structure of Human Deoxycytidine Kinase in complex with ADP and an inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.278 
  • R-Value Work: 0.220 
  • R-Value Observed: 0.223 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Lead optimization and structure-based design of potent and bioavailable deoxycytidine kinase inhibitors.

Jessop, T.C.Tarver, J.E.Carlsen, M.Xu, A.Healy, J.P.Heim-Riether, A.Fu, Q.Taylor, J.A.Augeri, D.J.Shen, M.Stouch, T.R.Swanson, R.V.Tari, L.W.Hunter, M.Hoffman, I.Keyes, P.E.Yu, X.C.Miranda, M.Liu, Q.Swaffield, J.C.David Kimball, S.Nouraldeen, A.Wilson, A.G.Foushee, A.M.Jhaver, K.Finch, R.Anderson, S.Oravecz, T.Carson, K.G.

(2009) Bioorg Med Chem Lett 19: 6784-6787

  • DOI: https://doi.org/10.1016/j.bmcl.2009.09.081
  • Primary Citation of Related Structures:  
    3IPX, 3IPY

  • PubMed Abstract: 

    A series of deoxycytidine kinase inhibitors was simultaneously optimized for potency and PK properties. A co-crystal structure then allowed merging this series with a high throughput screening hit to afford a highly potent, selective and orally bioavailable inhibitor, compound 10. This compound showed dose dependent inhibition of deoxycytidine kinase in vivo.


  • Organizational Affiliation

    Lexicon Pharmaceuticals, Princeton, NJ 08540, United States. tjessop@lexpharma.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Deoxycytidine kinase241Homo sapiensMutation(s): 0 
EC: 2.7.1.74
UniProt & NIH Common Fund Data Resources
Find proteins for P27707 (Homo sapiens)
Explore P27707 
Go to UniProtKB:  P27707
PHAROS:  P27707
GTEx:  ENSG00000156136 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP27707
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
B86 BindingDB:  3IPX IC50: min: 4000, max: 1.20e+5 (nM) from 2 assay(s)
PDBBind:  3IPX IC50: 120 (nM) from 1 assay(s)
Binding MOAD:  3IPX IC50: 120 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.278 
  • R-Value Work: 0.220 
  • R-Value Observed: 0.223 
  • Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 80.238α = 90
b = 80.238β = 90
c = 93.95γ = 90
Software Package:
Software NamePurpose
REFMACrefinement

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-08-18
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description