2OJI

Crystal structure of ERK2 in complex with N-benzyl-4-(4-(3-chlorophenyl)-1H-pyrazol-3-yl)-1H-pyrrole-2-carboxamide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.267 
  • R-Value Work: 0.209 
  • R-Value Observed: 0.215 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Flipped Out: Structure-Guided Design of Selective Pyrazolylpyrrole ERK Inhibitors.

Aronov, A.M.Baker, C.Bemis, G.W.Cao, J.Chen, G.Ford, P.J.Germann, U.A.Green, J.Hale, M.R.Jacobs, M.Janetka, J.W.Maltais, F.Martinez-Botella, G.Namchuk, M.N.Straub, J.Tang, Q.Xie, X.

(2007) J Med Chem 50: 1280-1287

  • DOI: https://doi.org/10.1021/jm061381f
  • Primary Citation of Related Structures:  
    2OJG, 2OJI, 2OJJ, 2OK1

  • PubMed Abstract: 

    The Ras/Raf/MEK/ERK signal transduction is a key oncogenic pathway implicated in a variety of human cancers. We have identified a novel series of pyrazolylpyrroles as inhibitors of ERK. Aided by the discovery of two distinct binding modes for the pyrazolylpyrrole scaffold, structure-guided optimization culminated in the discovery of 6p, a potent and selective inhibitor of ERK.


  • Organizational Affiliation

    Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge, Massachusetts 02139-4242, USA. alex_aronov@vrtx.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Mitogen-activated protein kinase 1380Homo sapiensMutation(s): 0 
Gene Names: MAPK1ERK2PRKM1
EC: 2.7.11.24
UniProt & NIH Common Fund Data Resources
Find proteins for P28482 (Homo sapiens)
Explore P28482 
Go to UniProtKB:  P28482
PHAROS:  P28482
GTEx:  ENSG00000100030 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP28482
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
33A
Query on 33A

Download Ideal Coordinates CCD File 
C [auth A]N-BENZYL-4-[4-(3-CHLOROPHENYL)-1H-PYRAZOL-3-YL]-1H-PYRROLE-2-CARBOXAMIDE
C21 H17 Cl N4 O
PDJZASCRQRBYQS-UHFFFAOYSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
B [auth A]SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Binding Affinity Annotations 
IDSourceBinding Affinity
33A BindingDB:  2OJI Ki: min: 85, max: 86 (nM) from 2 assay(s)
PDBBind:  2OJI Ki: 86 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.267 
  • R-Value Work: 0.209 
  • R-Value Observed: 0.215 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 48.557α = 90
b = 69.675β = 109.36
c = 59.986γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
PDB_EXTRACTdata extraction
CNXphasing
CNXrefinement

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


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: 2017-10-18
    Changes: Refinement description
  • Version 1.4: 2023-12-27
    Changes: Data collection, Database references, Derived calculations