2P3G

Crystal structure of a pyrrolopyridine inhibitor bound to MAPKAP Kinase-2


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.80 Å
  • R-Value Free: 0.374 
  • R-Value Work: 0.300 
  • R-Value Observed: 0.303 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Pyrrolopyridine Inhibitors of Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 (MK-2).

Anderson, D.R.Meyers, M.J.Vernier, W.F.Mahoney, M.W.Kurumbail, R.G.Caspers, N.Poda, G.I.Schindler, J.F.Reitz, D.B.Mourey, R.J.

(2007) J Med Chem 50: 2647-2654

  • DOI: https://doi.org/10.1021/jm0611004
  • Primary Citation of Related Structures:  
    2P3G

  • PubMed Abstract: 

    A new class of potent kinase inhibitors selective for mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP-K2 or MK-2) for the treatment of rheumatoid arthritis has been prepared and evaluated. These inhibitors have IC50 values as low as 10 nM against the target and have good selectivity profiles against a number of kinases including CDK2, ERK, JNK, and p38. These MK-2 inhibitors have been shown to suppress TNFalpha production in U397 cells and to be efficacious in an acute inflammation model. The structure-activity relationships of this series, the selectivity for MK-2 and their activity in both in vitro and in vivo models are discussed. The observed selectivity is discussed with the aid of an MK-2/inhibitor crystal structure.


  • Organizational Affiliation

    Pfizer Global Research and Development, St. Louis Laboratories, 700 Chesterfield Parkway W, Chesterfield, Missouri 63017, USA. david.r.anderson@pfizer.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
MAP kinase-activated protein kinase 2A [auth X]327Homo sapiensMutation(s): 0 
Gene Names: MAPKAPK2
EC: 2.7.11.1
UniProt & NIH Common Fund Data Resources
Find proteins for P49137 (Homo sapiens)
Explore P49137 
Go to UniProtKB:  P49137
PHAROS:  P49137
GTEx:  ENSG00000162889 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP49137
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
F10
Query on F10

Download Ideal Coordinates CCD File 
B [auth X]2-[2-(2-FLUOROPHENYL)PYRIDIN-4-YL]-1,5,6,7-TETRAHYDRO-4H-PYRROLO[3,2-C]PYRIDIN-4-ONE
C18 H14 F N3 O
XJJYJNMNYDNXNO-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
F10 BindingDB:  2P3G IC50: min: 126, max: 8900 (nM) from 3 assay(s)
EC50: min: 372, max: 2700 (nM) from 2 assay(s)
PDBBind:  2P3G IC50: 126 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.80 Å
  • R-Value Free: 0.374 
  • R-Value Work: 0.300 
  • R-Value Observed: 0.303 
  • Space Group: F 41 3 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 253.941α = 90
b = 253.941β = 90
c = 253.941γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
ADSCdata collection
HKL-2000data reduction
X-PLORphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-06-12
    Type: Initial release
  • Version 1.1: 2008-03-05
    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: 2024-02-21
    Changes: Data collection, Database references, Derived calculations