2PZY

Structure of MK2 Complexed with Compound 76


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.313 
  • R-Value Work: 0.251 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

The discovery of carboline analogs as potent MAPKAP-K2 inhibitors

Wu, J.-P.Wang, J.Abeywardane, A.Andersen, D.Emmanuel, M.Gautschi, E.Goldberg, D.R.Kashem, M.A.Lukas, S.Mao, W.Martin, L.Morwick, T.Moss, N.Pargellis, C.Patel, U.R.Patnaude, L.Peet, G.W.Skow, D.Snow, R.J.Ward, Y.Werneburg, B.White, A.

(2007) Bioorg Med Chem Lett 17: 4664-4669

  • DOI: https://doi.org/10.1016/j.bmcl.2007.05.101
  • Primary Citation of Related Structures:  
    2PZY

  • PubMed Abstract: 

    The discovery of a series of potent, carboline-based MK2 inhibitors is described. These compounds inhibit MK2 with IC50s as low as 10 nM, as measured in a DELFIA assay. An X-ray crystal structure reveals that they bind in a region near the p-loop and the hinge region of MK2a.


  • Organizational Affiliation

    Research and Development, Boehringer-Ingelheim Pharmaceuticals, 900 Ridgebury Road, Ridgefield, CT 06877, USA. jwu@rdg.boehringer-ingelheim.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
MAP kinase-activated protein kinase 2
A, B, C, D
324Homo 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 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
STU
Query on STU

Download Ideal Coordinates CCD File 
G [auth C]STAUROSPORINE
C28 H26 N4 O3
HKSZLNNOFSGOKW-FYTWVXJKSA-N
B18
Query on B18

Download Ideal Coordinates CCD File 
E [auth A],
F [auth B]
(4R)-N-[4-({[2-(DIMETHYLAMINO)ETHYL]AMINO}CARBONYL)-1,3-THIAZOL-2-YL]-4-METHYL-1-OXO-2,3,4,9-TETRAHYDRO-1H-BETA-CARBOLINE-6-CARBOXAMIDE
C21 H24 N6 O3 S
QWFFPYQWUWLDBV-NSHDSACASA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
B18 BindingDB:  2PZY IC50: 34 (nM) from 1 assay(s)
PDBBind:  2PZY IC50: 34 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.313 
  • R-Value Work: 0.251 
  • Space Group: P 63
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 159.61α = 90
b = 159.61β = 90
c = 134.5γ = 120
Software Package:
Software NamePurpose
d*TREKdata processing
CNSrefinement
PDB_EXTRACTdata extraction
CrystalCleardata collection
d*TREKdata reduction
d*TREKdata scaling
AMoREphasing

Structure Validation

View Full Validation Report



Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2007-07-31
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Derived calculations, Version format compliance
  • Version 1.2: 2024-02-21
    Changes: Data collection, Database references