PDBsum entry 2fys

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protein Protein-protein interface(s) links
Transferase PDB id
Jmol PyMol
Protein chains
338 a.a. *
11 a.a. *
Waters ×488
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Crystal structure of erk2 complex with kim peptide derived from mkp3
Structure: Mitogen-activated protein kinase 1. Chain: b, a. Synonym: extracellular signal-regulated kinase 2, erk-2, mitogen-activated protein kinase 2, map kinase 2, mapk 2, p42-mapk, ert1. Engineered: yes. Dual specificity protein phosphatase 6. Chain: d, c. Fragment: kim peptide, residues 60-76 (sws q64346).
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: mapk1, erk2, mapk, prkm1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: chemically synthesized.
Biol. unit: Tetramer (from PQS)
2.50Å     R-factor:   0.174     R-free:   0.266
Authors: S.Liu,J.P.Sun,B.Zhou,Z.Y.Zhang
Key ref:
S.Liu et al. (2006). Structural basis of docking interactions between ERK2 and MAP kinase phosphatase 3. Proc Natl Acad Sci U S A, 103, 5326-5331. PubMed id: 16567630 DOI: 10.1073/pnas.0510506103
08-Feb-06     Release date:   11-Apr-06    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P63086  (MK01_RAT) -  Mitogen-activated protein kinase 1
358 a.a.
338 a.a.
Protein chains
-  (POLG_HAVHM) - 
Protein chains
Pfam   ArchSchema ?
Q64346  (DUS6_RAT) -  Dual specificity protein phosphatase 6
381 a.a.
11 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: Chains B, A: E.C.  - Mitogen-activated protein kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
+ protein
+ phosphoprotein
   Enzyme class 2: Chains D, C: E.C.  - Protein-serine/threonine phosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: [a protein]-serine/threonine phosphate + H2O = [a protein]- serine/threonine + phosphate
[a protein]-serine/threonine phosphate
+ H(2)O
= [a protein]- serine/threonine
+ phosphate
   Enzyme class 3: Chains D, C: E.C.  - Protein-tyrosine-phosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Protein tyrosine phosphate + H2O = protein tyrosine + phosphate
Protein tyrosine phosphate
+ H(2)O
= protein tyrosine
+ phosphate
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     mitotic spindle   20 terms 
  Biological process     intracellular signal transduction   65 terms 
  Biochemical function     nucleotide binding     15 terms  


DOI no: 10.1073/pnas.0510506103 Proc Natl Acad Sci U S A 103:5326-5331 (2006)
PubMed id: 16567630  
Structural basis of docking interactions between ERK2 and MAP kinase phosphatase 3.
S.Liu, J.P.Sun, B.Zhou, Z.Y.Zhang.
Mitogen-activated protein (MAP) kinases are central components of signal transduction pathways for cell proliferation, stress responses, and differentiation. Signaling efficiency and specificity are modulated in large part by docking interactions between individual MAP kinase and the kinase interaction motif (KIM), (R/K)(2-3)-X(1-6)-Phi(A)-X-Phi(B), in its cognate kinases, phosphatases, scaffolding proteins, and substrates. We have determined the crystal structure of extracellular signal-regulated protein kinase 2 bound to the KIM peptide from MAP kinase phosphatase 3, an extracellular signal-regulated protein kinase 2-specific phosphatase. The structure reveals that the KIM docking site, situated in a noncatalytic region opposite of the kinase catalytic pocket, is comprised of a highly acidic patch and a hydrophobic groove, which engage the basic and Phi(A)-X-Phi(B) residues, respectively, in the KIM sequence. The specific docking interactions observed in the structure consolidate all known biochemical data. In addition, structural comparison indicates that the KIM docking site is conserved in all MAP kinases. The results establish a structural model for understanding how MAP kinases interact with their regulators and substrates and provide new insights into how MAP kinase docking specificity can be achieved.
  Selected figure(s)  
Figure 2.
Fig. 2. Detailed interactions between ERK2 and KIM^MKP3. (a) Surface representation of ERK2 in complex with KIM^MKP3, colored by electrostatic potential. KIM residues are in black, and ERK2 residues are in light blue. (b) Stereo diagram of the docking interactions between ERK2 (orange) and KIM^MKP3 (green). ERK2 residues are shown in black, and those of KIM^MKP3 are shown in green.
Figure 4.
Fig. 4. Structural comparison of the ERK2, p38 , and JNK1 docking sites. (a) Structural comparison of the hydrophobic groove in ERK2 (green), p38 (orange), and JNK1 (cyan). ERK2 residues that contribute to hydrophobic interactions with the [A] and [B] residues are shown. (b) Structural comparison of the acidic patch in ERK2 (green), p38 (orange), and JNK1 (cyan). ERK2 residues that interact directly with the basic residues are shown.
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22307056 M.O.Kim, S.H.Kim, Y.Y.Cho, J.Nadas, C.H.Jeong, K.Yao, D.J.Kim, D.H.Yu, Y.S.Keum, K.Y.Lee, Z.Huang, A.M.Bode, and Z.Dong (2012).
ERK1 and ERK2 regulate embryonic stem cell self-renewal through phosphorylation of Klf4.
  Nat Struct Mol Biol, 19, 283-290.  
21494553 S.Lee, M.Warthaka, C.Yan, T.S.Kaoud, A.Piserchio, R.Ghose, P.Ren, and K.N.Dalby (2011).
A model of a MAPK•substrate complex in an active conformation: a computational and experimental approach.
  PLoS One, 6, e18594.  
21134636 R.Akella, X.Min, Q.Wu, K.H.Gardner, and E.J.Goldsmith (2010).
The third conformation of p38α MAP kinase observed in phosphorylated p38α and in solution.
  Structure, 18, 1571-1578.
PDB code: 3p4k
19196711 A.J.Bardwell, E.Frankson, and L.Bardwell (2009).
Selectivity of docking sites in MAPK kinases.
  J Biol Chem, 284, 13165-13173.  
19424502 M.C.Balasu, L.N.Spiridon, S.Miron, C.T.Craescu, A.J.Scheidig, A.J.Petrescu, and S.E.Szedlacsek (2009).
Interface analysis of the complex between ERK2 and PTP-SL.
  PLoS ONE, 4, e5432.  
19141286 X.Min, R.Akella, H.He, J.M.Humphreys, S.E.Tsutakawa, S.J.Lee, J.A.Tainer, M.H.Cobb, and E.J.Goldsmith (2009).
The structure of the MAP2K MEK6 reveals an autoinhibitory dimer.
  Structure, 17, 96.
PDB code: 3enm
18855677 A.Bakan, J.S.Lazo, P.Wipf, K.M.Brummond, and I.Bahar (2008).
Toward a molecular understanding of the interaction of dual specificity phosphatases with substrates: insights from structure-based modeling and high throughput screening.
  Curr Med Chem, 15, 2536-2544.  
18753132 M.Maillet, N.H.Purcell, M.A.Sargent, A.J.York, O.F.Bueno, and J.D.Molkentin (2008).
DUSP6 (MKP3) null mice show enhanced ERK1/2 phosphorylation at baseline and increased myocyte proliferation in the heart affecting disease susceptibility.
  J Biol Chem, 283, 31246-31255.  
18068683 R.Akella, T.M.Moon, and E.J.Goldsmith (2008).
Unique MAP Kinase binding sites.
  Biochim Biophys Acta, 1784, 48-55.  
18298792 R.Pulido, and R.Hooft van Huijsduijnen (2008).
Protein tyrosine phosphatases: dual-specificity phosphatases in health and disease.
  FEBS J, 275, 848-866.  
17496919 A.G.Turjanski, J.P.Vaqué, and J.S.Gutkind (2007).
MAP kinases and the control of nuclear events.
  Oncogene, 26, 3240-3253.  
17532509 B.Zhou, and Z.Y.Zhang (2007).
Application of hydrogen/deuterium exchange mass spectrometry to study protein tyrosine phosphatase dynamics, ligand binding, and substrate specificity.
  Methods, 42, 227-233.  
17496916 D.M.Owens, and S.M.Keyse (2007).
Differential regulation of MAP kinase signalling by dual-specificity protein phosphatases.
  Oncogene, 26, 3203-3213.  
17709754 N.H.Purcell, B.J.Wilkins, A.York, M.K.Saba-El-Leil, S.Meloche, J.Robbins, and J.D.Molkentin (2007).
Genetic inhibition of cardiac ERK1/2 promotes stress-induced apoptosis and heart failure but has no effect on hypertrophy in vivo.
  Proc Natl Acad Sci U S A, 104, 14074-14079.  
17658891 O.Abramczyk, M.A.Rainey, R.Barnes, L.Martin, and K.N.Dalby (2007).
Expanding the repertoire of an ERK2 recruitment site: cysteine footprinting identifies the D-recruitment site as a mediator of Ets-1 binding.
  Biochemistry, 46, 9174-9186.  
17079133 A.Reményi, M.C.Good, and W.A.Lim (2006).
Docking interactions in protein kinase and phosphatase networks.
  Curr Opin Struct Biol, 16, 676-685.  
17000106 F.Chen, C.N.Hancock, A.T.Macias, J.Joh, K.Still, S.Zhong, A.D.MacKerell, and P.Shapiro (2006).
Characterization of ATP-independent ERK inhibitors identified through in silico analysis of the active ERK2 structure.
  Bioorg Med Chem Lett, 16, 6281-6287.  
16884917 L.Bardwell, and K.Shah (2006).
Analysis of mitogen-activated protein kinase activation and interactions with regulators and substrates.
  Methods, 40, 213-223.  
17052210 L.Bardwell (2006).
Mechanisms of MAPK signalling specificity.
  Biochem Soc Trans, 34, 837-841.  
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.