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PDBsum entry 1gol

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protein ligands metals links
Transferase PDB id
1gol
Jmol
Contents
Protein chain
357 a.a. *
Ligands
ATP
Metals
_MG
Waters ×79
* Residue conservation analysis
PDB id:
1gol
Name: Transferase
Title: Coordinates of rat map kinase erk2 with an arginine mutation at position 52
Structure: Extracellular regulated kinase 2. Chain: a. Synonym: map kinase erk2. Engineered: yes. Mutation: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Cell_line: bl21. Gene: erk2. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
2.80Å     R-factor:   not given    
Authors: P.C.Harkins,F.Zhang,E.J.Goldsmith
Key ref:
M.J.Robinson et al. (1996). Mutation of position 52 in ERK2 creates a nonproductive binding mode for adenosine 5'-triphosphate. Biochemistry, 35, 5641-5646. PubMed id: 8639522 DOI: 10.1021/bi952723e
Date:
23-Jan-96     Release date:   12-Mar-97    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P63086  (MK01_RAT) -  Mitogen-activated protein kinase 1
Seq:
Struc:
358 a.a.
357 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 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
Bound ligand (Het Group name = ATP)
corresponds exactly
+ protein
= ADP
+ phosphoprotein
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     mitotic spindle   21 terms 
  Biological process     intracellular signal transduction   40 terms 
  Biochemical function     nucleotide binding     15 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi952723e Biochemistry 35:5641-5646 (1996)
PubMed id: 8639522  
 
 
Mutation of position 52 in ERK2 creates a nonproductive binding mode for adenosine 5'-triphosphate.
M.J.Robinson, P.C.Harkins, J.Zhang, R.Baer, J.W.Haycock, M.H.Cobb, E.J.Goldsmith.
 
  ABSTRACT  
 
Among the protein kinases, an absolutely conserved lysine in subdomain II is required for high catalytic activity. This lysine is known to interact with the substrate ATP, but otherwise its role is not well understood. We have used biochemical and structural methods to investigate the function of this lysine (K52) in phosphoryl transfer reactions catalyzed by the MAP kinase ERK2. The kinetic properties of activated wild-type ERK2 and K52 mutants were examined using the oncoprotein TAL2, myelin basic protein, and a designed synthetic peptide as substrates. The catalytic activities of K52R and K52A ERK2 were lower than that of wild-type ERK2, primarily as a consequence of reductions in kcat. Further, there was little difference in Km for ATP, but the Km,app for peptide substrate was higher for the K52 mutants. The three-dimensional structure of unphosphorylated K52R ERK2 in the absence and presence of bound ATP was determined and compared with the structure of unphosphorylated wild-type ERK2. ATP adopted a well-defined but distinct binding mode in K52R ERK2 compared to the binding mode in the wild-type enzyme. The structural and kinetic data show that mutation of K52 created a nonproductive binding mode for ATP and suggest that K52 is essential for orienting ATP for catalysis.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21474065 N.Jura, X.Zhang, N.F.Endres, M.A.Seeliger, T.Schindler, and J.Kuriyan (2011).
Catalytic control in the EGF receptor and its connection to general kinase regulatory mechanisms.
  Mol Cell, 42, 9.  
20519540 S.D.Iñiguez, V.Vialou, B.L.Warren, J.L.Cao, L.F.Alcantara, L.C.Davis, Z.Manojlovic, R.L.Neve, S.J.Russo, M.H.Han, E.J.Nestler, and C.A.Bolaños-Guzmán (2010).
Extracellular signal-regulated kinase-2 within the ventral tegmental area regulates responses to stress.
  J Neurosci, 30, 7652-7663.  
20421461 S.S.Taylor, and A.P.Kornev (2010).
Yet another "active" pseudokinase, Erb3.
  Proc Natl Acad Sci U S A, 107, 8047-8048.  
19361221 A.G.Turjanski, G.Hummer, and J.S.Gutkind (2009).
How mitogen-activated protein kinases recognize and phosphorylate their targets: A QM/MM study.
  J Am Chem Soc, 131, 6141-6148.  
19290920 B.B.Au-Yeung, S.Deindl, L.Y.Hsu, E.H.Palacios, S.E.Levin, J.Kuriyan, and A.Weiss (2009).
The structure, regulation, and function of ZAP-70.
  Immunol Rev, 228, 41-57.  
19879846 S.Hu, Z.Xie, A.Onishi, X.Yu, L.Jiang, J.Lin, H.S.Rho, C.Woodard, H.Wang, J.S.Jeong, S.Long, X.He, H.Wade, S.Blackshaw, J.Qian, and H.Zhu (2009).
Profiling the human protein-DNA interactome reveals ERK2 as a transcriptional repressor of interferon signaling.
  Cell, 139, 610-622.  
19120698 W.Wang, Y.Yang, Y.Gao, Q.Xu, F.Wang, S.Zhu, W.Old, K.Resing, N.Ahn, M.Lei, and X.Liu (2009).
Structural and mechanistic insights into Mps1 kinase activation.
  J Cell Mol Med, 13, 1679-1694.
PDB code: 3dbq
18004777 K.Anamika, A.Bhattacharya, and N.Srinivasan (2008).
Analysis of the protein kinome of Entamoeba histolytica.
  Proteins, 71, 995.  
17496912 A.Clapéron, and M.Therrien (2007).
KSR and CNK: two scaffolds regulating RAS-mediated RAF activation.
  Oncogene, 26, 3143-3158.  
17167778 B.E.Bobick, T.M.Thornhill, and W.M.Kulyk (2007).
Fibroblast growth factors 2, 4, and 8 exert both negative and positive effects on limb, frontonasal, and mandibular chondrogenesis via MEK-ERK activation.
  J Cell Physiol, 211, 233-243.  
17694525 D.Kuhn, N.Weskamp, E.Hüllermeier, and G.Klebe (2007).
Functional Classification of Protein Kinase Binding Sites Using Cavbase.
  ChemMedChem, 2, 1432-1447.  
17912359 J.D.Knight, B.Qian, D.Baker, and R.Kothary (2007).
Conservation, variability and the modeling of active protein kinases.
  PLoS ONE, 2, e982.  
17353359 L.W.Tam, N.F.Wilson, and P.A.Lefebvre (2007).
A CDK-related kinase regulates the length and assembly of flagella in Chlamydomonas.
  J Cell Biol, 176, 819-829.  
  17918909 N.Fernandes, D.E.Bailey, D.L.Vanvranken, and N.L.Allbritton (2007).
Use of docking peptides to design modular substrates with high efficiency for mitogen-activated protein kinase extracellular signal-regulated kinase.
  ACS Chem Biol, 2, 665-673.  
17355172 N.Kannan, S.S.Taylor, Y.Zhai, J.C.Venter, and G.Manning (2007).
Structural and functional diversity of the microbial kinome.
  PLoS Biol, 5, e17.  
17371162 T.T.Tsai, A.Guttapalli, A.Agrawal, T.J.Albert, I.M.Shapiro, and M.V.Risbud (2007).
MEK/ERK signaling controls osmoregulation of nucleus pulposus cells of the intervertebral disc by transactivation of TonEBP/OREBP.
  J Bone Miner Res, 22, 965-974.  
16805921 C.Vantaggiato, I.Formentini, A.Bondanza, C.Bonini, L.Naldini, and R.Brambilla (2006).
ERK1 and ERK2 mitogen-activated protein kinases affect Ras-dependent cell signaling differentially.
  J Biol, 5, 14.  
16362034 F.Qiao, B.Harada, H.Song, J.Whitelegge, A.J.Courey, and J.U.Bowie (2006).
Mae inhibits Pointed-P2 transcriptional activity by blocking its MAPK docking site.
  EMBO J, 25, 70-79.  
16866353 P.A.Lemaire, I.Tessmer, R.Craig, D.A.Erie, and J.L.Cole (2006).
Unactivated PKR exists in an open conformation capable of binding nucleotides.
  Biochemistry, 45, 9074-9084.  
17020917 P.Sacchetti, R.Carpentier, P.Ségard, C.Olivé-Cren, and P.Lefebvre (2006).
Multiple signaling pathways regulate the transcriptional activity of the orphan nuclear receptor NURR1.
  Nucleic Acids Res, 34, 5515-5527.  
16799155 S.Polychronopoulos, M.Verykokakis, M.N.Yazicioglu, M.Sakarellos-Daitsiotis, M.H.Cobb, and G.Mavrothalassitis (2006).
The transcriptional ETS2 repressor factor associates with active and inactive Erks through distinct FXF motifs.
  J Biol Chem, 281, 25601-25611.  
15893667 M.Lei, M.A.Robinson, and S.C.Harrison (2005).
The active conformation of the PAK1 kinase domain.
  Structure, 13, 769-778.
PDB codes: 1yhv 1yhw
15466470 Z.Huang, B.Zhou, and Z.Y.Zhang (2004).
Molecular determinants of substrate recognition in hematopoietic protein-tyrosine phosphatase.
  J Biol Chem, 279, 52150-52159.  
12842015 S.A.Berman, N.F.Wilson, N.A.Haas, and P.A.Lefebvre (2003).
A novel MAP kinase regulates flagellar length in Chlamydomonas.
  Curr Biol, 13, 1145-1149.  
11839761 B.Zhou, and Z.Y.Zhang (2002).
The activity of the extracellular signal-regulated kinase 2 is regulated by differential phosphorylation in the activation loop.
  J Biol Chem, 277, 13889-13899.  
12016217 C.A.Chrestensen, and T.W.Sturgill (2002).
Characterization of the p90 ribosomal S6 kinase 2 carboxyl-terminal domain as a protein kinase.
  J Biol Chem, 277, 27733-27741.  
11782450 J.J.Seidel, and B.J.Graves (2002).
An ERK2 docking site in the Pointed domain distinguishes a subset of ETS transcription factors.
  Genes Dev, 16, 127-137.  
12093731 J.Samaj, M.Ovecka, A.Hlavacka, F.Lecourieux, I.Meskiene, I.Lichtscheidl, P.Lenart, J.Salaj, D.Volkmann, L.Bögre, F.Baluska, and H.Hirt (2002).
Involvement of the mitogen-activated protein kinase SIMK in regulation of root hair tip growth.
  EMBO J, 21, 3296-3306.  
11668177 M.G.Callow, F.Clairvoyant, S.Zhu, B.Schryver, D.B.Whyte, J.R.Bischoff, B.Jallal, and T.Smeal (2002).
Requirement for PAK4 in the anchorage-independent growth of human cancer cell lines.
  J Biol Chem, 277, 550-558.  
11395417 B.Vanhaesebroeck, S.J.Leevers, K.Ahmadi, J.Timms, R.Katso, P.C.Driscoll, R.Woscholski, P.J.Parker, and M.D.Waterfield (2001).
Synthesis and function of 3-phosphorylated inositol lipids.
  Annu Rev Biochem, 70, 535-602.  
11389851 H.Yamaguchi, M.Matsushita, A.C.Nairn, and J.Kuriyan (2001).
Crystal structure of the atypical protein kinase domain of a TRP channel with phosphotransferase activity.
  Mol Cell, 7, 1047-1057.
PDB codes: 1ia9 1iah 1iaj
10821702 C.N.Prowse, J.C.Hagopian, M.H.Cobb, N.G.Ahn, and J.Lew (2000).
Catalytic reaction pathway for the mitogen-activated protein kinase ERK2.
  Biochemistry, 39, 6258-6266.  
10889467 D.Fox, and A.G.Smulian (2000).
Mkp1 of Pneumocystis carinii associates with the yeast transcription factor Rlm1 via a mechanism independent of the activation state.
  Cell Signal, 12, 381-390.  
10713991 K.A.Denessiouk, and M.S.Johnson (2000).
When fold is not important: a common structural framework for adenine and AMP binding in 12 unrelated protein families.
  Proteins, 38, 310-326.  
10644696 S.Himpel, W.Tegge, R.Frank, S.Leder, H.G.Joost, and W.Becker (2000).
Specificity determinants of substrate recognition by the protein kinase DYRK1A.
  J Biol Chem, 275, 2431-2438.  
9890950 D.A.Enke, P.Kaldis, J.K.Holmes, and M.J.Solomon (1999).
The CDK-activating kinase (Cak1p) from budding yeast has an unusual ATP-binding pocket.
  J Biol Chem, 274, 1949-1956.  
10384963 R.Tamaskovic, P.Forrer, and R.Jaussi (1999).
Enzyme-linked immunosorbent assay for the measurement of JNK activity in cell extracts.
  Biol Chem, 380, 569-578.  
  9819406 F.Walker, A.Kato, L.J.Gonez, M.L.Hibbs, N.Pouliot, A.Levitzki, and A.W.Burgess (1998).
Activation of the Ras/mitogen-activated protein kinase pathway by kinase-defective epidermal growth factor receptors results in cell survival but not proliferation.
  Mol Cell Biol, 18, 7192-7204.  
9799732 M.J.Robinson, S.A.Stippec, E.Goldsmith, M.A.White, and M.H.Cobb (1998).
A constitutively active and nuclear form of the MAP kinase ERK2 is sufficient for neurite outgrowth and cell transformation.
  Curr Biol, 8, 1141-1150.  
  9243503 A.A.Reszka, J.C.Bulinski, E.G.Krebs, and E.H.Fischer (1997).
Mitogen-activated protein kinase/extracellular signal-regulated kinase 2 regulates cytoskeletal organization and chemotaxis via catalytic and microtubule-specific interactions.
  Mol Biol Cell, 8, 1219-1232.  
9434895 F.Sicheri, and J.Kuriyan (1997).
Structures of Src-family tyrosine kinases.
  Curr Opin Struct Biol, 7, 777-785.  
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 code is shown on the right.