3KGA

Crystal structure of MAPKAP kinase 2 (MK2) complexed with a potent 3-aminopyrazole ATP site inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.55 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.180 
  • R-Value Observed: 0.183 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Novel 3-aminopyrazole inhibitors of MK-2 discovered by scaffold hopping strategy.

Velcicky, J.Feifel, R.Hawtin, S.Heng, R.Huppertz, C.Koch, G.Kroemer, M.Moebitz, H.Revesz, L.Scheufler, C.Schlapbach, A.

(2010) Bioorg Med Chem Lett 20: 1293-1297

  • DOI: https://doi.org/10.1016/j.bmcl.2009.10.138
  • Primary Citation of Related Structures:  
    3KGA

  • PubMed Abstract: 

    New, selective 3-aminopyrazole based MK2-inhibitors were discovered by scaffold hopping strategy. The new derivatives proved to inhibit intracellular phosphorylation of hsp27 as well as LPS-induced TNFalpha release in cells. In addition, selected derivative 14e also inhibited LPS-induced TNFalpha release in vivo.


  • Organizational Affiliation

    Novartis Institutes for BioMedical Research, CH-4002 Basel, Switzerland. juraj.velcicky@novartis.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
MAP kinase-activated protein kinase 2299Homo sapiensMutation(s): 1 
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 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
LX9
Query on LX9

Download Ideal Coordinates CCD File 
C [auth A]6-{3-amino-1-[3-(1H-indol-6-yl)phenyl]-1H-pyrazol-4-yl}-3,4-dihydroisoquinolin-1(2H)-one
C26 H21 N5 O
ZTKOUSVWVUFWQC-UHFFFAOYSA-N
MG
Query on MG

Download Ideal Coordinates CCD File 
B [auth A]MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
LX9 PDBBind:  3KGA IC50: 61 (nM) from 1 assay(s)
BindingDB:  3KGA IC50: 61 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.55 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.180 
  • R-Value Observed: 0.183 
  • Space Group: P 63 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 103.12α = 90
b = 103.12β = 90
c = 165.415γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
XSCALEdata scaling
REFMACphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-01-26
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2021-10-13
    Changes: Database references, Derived calculations
  • Version 1.3: 2024-02-21
    Changes: Data collection