2OBJ

Crystal structure of human PIM-1 Kinase in complex with inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.246 
  • R-Value Work: 0.205 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Identification and structure-activity relationships of substituted pyridones as inhibitors of Pim-1 kinase.

Cheney, I.W.Yan, S.Appleby, T.Walker, H.Vo, T.Yao, N.Hamatake, R.Hong, Z.Wu, J.Z.

(2007) Bioorg Med Chem Lett 17: 1679-1683

  • DOI: https://doi.org/10.1016/j.bmcl.2006.12.086
  • Primary Citation of Related Structures:  
    2OBJ

  • PubMed Abstract: 

    A novel series of highly potent substituted pyridone Pim-1 kinase inhibitors is described. Structural requirements for in vitro activity are outlined as well as a complex crystal structure with the most potent Pim-1 inhibitor reported (IC(50)=50 nM). A hydrogen bond matrix involving the Pim-1 inhibitor, two water molecules, and the catalytic core, together with a potential weak hydrogen bond between an aromatic hydrogen on the R(1) phenyl ring and a main-chain carbonyl of Pim-1, accounts for the overall potency of this inhibitor.


  • Organizational Affiliation

    Valeant Pharmaceuticals Research and Development, 3300 Hyland Avenue, Costa Mesa, CA 92626, USA. wcheney@ardeabiosciences.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Proto-oncogene serine/threonine-protein kinase Pim-1333Homo sapiensMutation(s): 1 
EC: 2.7.11.1
UniProt & NIH Common Fund Data Resources
Find proteins for P11309 (Homo sapiens)
Explore P11309 
Go to UniProtKB:  P11309
PHAROS:  P11309
GTEx:  ENSG00000137193 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP11309
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
VRV
Query on VRV

Download Ideal Coordinates CCD File 
B [auth A]6-(5-BROMO-2-HYDROXYPHENYL)-2-OXO-4-PHENYL-1,2-DIHYDROPYRIDINE-3-CARBONITRILE
C18 H11 Br N2 O2
SVSYJTYGPLVUOZ-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
SEP
Query on SEP
A
L-PEPTIDE LINKINGC3 H8 N O6 PSER
Binding Affinity Annotations 
IDSourceBinding Affinity
VRV Binding MOAD:  2OBJ IC50: 50 (nM) from 1 assay(s)
BindingDB:  2OBJ IC50: 50 (nM) from 1 assay(s)
PDBBind:  2OBJ IC50: 50 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.246 
  • R-Value Work: 0.205 
  • Space Group: P 65
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 97.264α = 90
b = 97.264β = 90
c = 80.827γ = 120
Software Package:
Software NamePurpose
CrystalCleardata collection
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling
CNSphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-02-06
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-08-30
    Changes: Data collection, Database references, Derived calculations, Refinement description