2GTM

Mutated Mouse P38 MAP Kinase Domain in complex with Inhibitor PG-892579


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.261 
  • R-Value Work: 0.212 
  • R-Value Observed: 0.214 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

The development of novel C-2, C-8, and N-9 trisubstituted purines as inhibitors of TNF-alpha production.

Sabat, M.Vanrens, J.C.Clark, M.P.Brugel, T.A.Maier, J.Bookland, R.G.Laufersweiler, M.J.Laughlin, S.K.Golebiowski, A.De, B.Hsieh, L.C.Walter, R.L.Mekel, M.J.Janusz, M.J.

(2006) Bioorg Med Chem Lett 16: 4360-4365

  • DOI: https://doi.org/10.1016/j.bmcl.2006.05.050
  • Primary Citation of Related Structures:  
    2GTM, 2GTN

  • PubMed Abstract: 

    A series of C-2, C-8, and N-9 trisubstituted purine based inhibitors of TNF-alpha production are described. The most potent analogs showed low nanomolar activity against LPS-induced TNF-alpha production in a THP-1 cell based assay. The SAR of the series was optimized with the aid of X-ray co-crystal structures of these inhibitors bound with mutated p38 (mp38).


  • Organizational Affiliation

    Procter and Gamble Pharmaceuticals, Health Care Research Center, Mason, OH 45040, USA. sabat.mp@pg.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Mitogen-activated protein kinase 14348Mus musculusMutation(s): 0 
Gene Names: Mapk14
EC: 2.7.11.24
UniProt
Find proteins for P47811 (Mus musculus)
Explore P47811 
Go to UniProtKB:  P47811
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP47811
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
LID
Query on LID

Download Ideal Coordinates CCD File 
B [auth A]8-(2-CHLOROPHENYLAMINO)-2-(2,6-DIFLUOROPHENYLAMINO)-9-ETHYL-9H-PURINE-1,7-DIIUM
C19 H15 Cl F2 N6
ZWKOUFZHPNIQSH-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
LID Binding MOAD:  2GTM IC50: 542 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.261 
  • R-Value Work: 0.212 
  • R-Value Observed: 0.214 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 63.876α = 90
b = 73.627β = 90
c = 76.16γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing
REFMACrefinement
PDB_EXTRACTdata extraction
MAR345data collection
HKL-2000data 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: 2006-05-23
    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: 2017-10-18
    Changes: Refinement description
  • Version 1.4: 2024-02-14
    Changes: Data collection, Database references, Derived calculations