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PDBsum entry 2ojj

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Transferase PDB id
2ojj
Jmol
Contents
Protein chain
344 a.a. *
Ligands
SO4
82A
Waters ×59
* Residue conservation analysis
PDB id:
2ojj
Name: Transferase
Title: Crystal structure of erk2 in complex with (s)-n-(1-(3- chloro-4-fluorophenyl)-2-hydroxyethyl)-4-(4-(3- chlorophenyl)-1h-pyrazol-3-yl)-1h-pyrrole-2-carboxamide
Structure: Mitogen-activated protein kinase 1. Chain: a. Synonym: extracellular signal-regulated kinase 2, erk-2, mitogen-activated protein kinase 2, map kinase 2, mapk 2, p42-mapk, ert1. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: mapk1, erk2, prkm1. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.40Å     R-factor:   0.215     R-free:   0.268
Authors: X.Xie,M.D.Jacobs
Key ref: A.M.Aronov et al. (2007). Flipped out: structure-guided design of selective pyrazolylpyrrole ERK inhibitors. J Med Chem, 50, 1280-1287. PubMed id: 17300186 DOI: 10.1021/jm061381f
Date:
12-Jan-07     Release date:   06-Feb-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P28482  (MK01_HUMAN) -  Mitogen-activated protein kinase 1
Seq:
Struc:
360 a.a.
344 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.7.11.24  - Mitogen-activated protein kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
ATP
+ protein
= ADP
+ phosphoprotein
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     protein complex   21 terms 
  Biological process     viral reproduction   73 terms 
  Biochemical function     nucleotide binding     15 terms  

 

 
    reference    
 
 
DOI no: 10.1021/jm061381f J Med Chem 50:1280-1287 (2007)
PubMed id: 17300186  
 
 
Flipped out: structure-guided design of selective pyrazolylpyrrole ERK inhibitors.
A.M.Aronov, C.Baker, G.W.Bemis, J.Cao, G.Chen, P.J.Ford, U.A.Germann, J.Green, M.R.Hale, M.Jacobs, J.W.Janetka, F.Maltais, G.Martinez-Botella, M.N.Namchuk, J.Straub, Q.Tang, X.Xie.
 
  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.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21110380 J.L.Yap, S.Worlikar, A.D.MacKerell, P.Shapiro, and S.Fletcher (2011).
Small-molecule inhibitors of the ERK signaling pathway: Towards novel anticancer therapeutics.
  ChemMedChem, 6, 38-48.  
20818420 R.Y.Huang, M.Y.Li, M.K.Hsin, M.J.Underwood, L.T.Ma, T.S.Mok, T.D.Warner, and G.G.Chen (2011).
4-Methylnitrosamino-1-3-pyridyl-1-butanone (NNK) promotes lung cancer cell survival by stimulating thromboxane A2 and its receptor.
  Oncogene, 30, 106-116.  
20482377 S.Ramaswamy, I.Yen, S.Sideris, S.Malek, and C.E.Heise (2010).
A plate-based assay to measure cellular ERK substrate phosphorylation: utility for drug discovery of the MAPK-signaling cascade.
  Assay Drug Dev Technol, 8, 497-503.  
20045950 T.Shen, J.Lee, E.Lee, S.H.Kim, T.W.Kim, and J.Y.Cho (2010).
Cafestol, a coffee-specific diterpene, is a novel extracellular signal-regulated kinase inhibitor with AP-1-targeted inhibition of prostaglandin E2 production in lipopolysaccharide-activated macrophages.
  Biol Pharm Bull, 33, 128-132.  
19689374 K.Burkhard, S.Smith, R.Deshmukh, A.D.MacKerell, and P.Shapiro (2009).
Development of extracellular signal-regulated kinase inhibitors.
  Curr Top Med Chem, 9, 678-689.  
19261605 T.Kamenecka, J.Habel, D.Duckett, W.Chen, Y.Y.Ling, B.Frackowiak, R.Jiang, Y.Shin, X.Song, and P.Lograsso (2009).
Structure-Activity Relationships and X-ray Structures Describing the Selectivity of Aminopyrazole Inhibitors for c-Jun N-terminal Kinase 3 (JNK3) over p38.
  J Biol Chem, 284, 12853-12861.
PDB codes: 3fi2 3fi3
19356729 Y.Kim, K.Kim, H.Lee, S.Han, Y.S.Lee, J.Choe, Y.M.Kim, J.H.Hahn, J.Y.Ro, and D.Jeoung (2009).
Celastrol binds to ERK and inhibits FcepsilonRI signaling to exert an anti-allergic effect.
  Eur J Pharmacol, 612, 131-142.  
19105050 F.Chen, A.D.Mackerell, Y.Luo, and P.Shapiro (2008).
Using Caenorhabditis elegans as a model organism for evaluating extracellular signal-regulated kinase docking domain inhibitors.
  J Cell Commun Signal, 2, 81-92.  
18663490 Y.Z.Xiong, and P.Y.Chen (2008).
ONIOM DFT/PM3 calculation on the interaction between STI-571 and abelson tyrosine kinase.
  J Mol Model, 14, 1083-1086.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.