spacer
spacer

PDBsum entry 3i5z

Go to PDB code: 
protein ligands links
Transferase PDB id
3i5z
Jmol
Contents
Protein chain
331 a.a. *
Ligands
SO4 ×4
Z48
Waters ×165
* Residue conservation analysis
PDB id:
3i5z
Name: Transferase
Title: Crystal structure of erk2 bound to (s)-n-(2-hydroxy-1-phenyl (5-methyl-2-(phenylamino)pyrimidin-4-yl)-1h-pyrrole-2-carbo
Structure: Mitogen-activated protein kinase 1. Chain: a. Synonym: extracellular signal-regulated kinase 2, erk-2, mi activated protein kinase 2, map kinase 2, mapk 2, p42-mapk, engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: erk2, mapk1, prkm1, prkm2. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.20Å     R-factor:   0.217     R-free:   0.258
Authors: M.D.Jacobs,X.Xie
Key ref: A.M.Aronov et al. (2009). Structure-guided design of potent and selective pyrimidylpyrrole inhibitors of extracellular signal-regulated kinase (ERK) using conformational control. J Med Chem, 52, 6362-6368. PubMed id: 19827834
Date:
06-Jul-09     Release date:   12-Jan-10    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P28482  (MK01_HUMAN) -  Mitogen-activated protein kinase 1
Seq:
Struc:
360 a.a.
331 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   20 terms 
  Biological process     viral reproduction   73 terms 
  Biochemical function     nucleotide binding     15 terms  

 

 
    reference    
 
 
J Med Chem 52:6362-6368 (2009)
PubMed id: 19827834  
 
 
Structure-guided design of potent and selective pyrimidylpyrrole inhibitors of extracellular signal-regulated kinase (ERK) using conformational control.
A.M.Aronov, Q.Tang, G.Martinez-Botella, G.W.Bemis, J.Cao, G.Chen, N.P.Ewing, P.J.Ford, U.A.Germann, J.Green, M.R.Hale, M.Jacobs, J.W.Janetka, F.Maltais, W.Markland, M.N.Namchuk, S.Nanthakumar, S.Poondru, J.Straub, E.ter Haar, X.Xie.
 
  ABSTRACT  
 
The Ras/Raf/MEK/ERK signal transduction, an oncogenic pathway implicated in a variety of human cancers, is a key target in anticancer drug design. A novel series of pyrimidylpyrrole ERK inhibitors has been identified. Discovery of a conformational change for lead compound 2, when bound to ERK2 relative to antitarget GSK3, enabled structure-guided selectivity optimization, which led to the discovery of 11e, a potent, selective, and orally bioavailable 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.  
  21469159 S.Y.Lu, Y.J.Jiang, J.Lv, J.W.Zou, and T.X.Wu (2011).
Role of bridging water molecules in GSK3β-inhibitor complexes: insights from QM/MM, MD, and molecular docking studies.
  J Comput Chem, 32, 1907-1918.  
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.