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Hydrolase/inhibitor PDB id
2o8g
Jmol
Contents
Protein chains
295 a.a. *
59 a.a. *
Metals
_MN ×2
Waters ×243
* Residue conservation analysis
PDB id:
2o8g
Name: Hydrolase/inhibitor
Title: Rat pp1c gamma complexed with mouse inhibitor-2
Structure: Serine/threonine-protein phosphatase pp1-gamma ca subunit. Chain: a, b. Synonym: pp-1g, protein phosphatase 1c catalytic subunit. Engineered: yes. Protein phosphatase inhibitor 2. Chain: i, j. Synonym: ipp-2. Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: ppp1cc. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Mus musculus. House mouse. Organism_taxid: 10090.
Resolution:
2.50Å     R-factor:   0.197     R-free:   0.235
Authors: T.D.Hurley
Key ref:
T.D.Hurley et al. (2007). Structural basis for regulation of protein phosphatase 1 by inhibitor-2. J Biol Chem, 282, 28874-28883. PubMed id: 17636256 DOI: 10.1074/jbc.M703472200
Date:
12-Dec-06     Release date:   17-Jul-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P63088  (PP1G_RAT) -  Serine/threonine-protein phosphatase PP1-gamma catalytic subunit
Seq:
Struc: 		323 a.a.
295 a.a.
Protein chains
Pfam   ArchSchema ?
Q9DCL8  (IPP2_MOUSE) -  Protein phosphatase inhibitor 2
Seq:
Struc: 		206 a.a.
59 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 19 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chains A, B: E.C.3.1.3.16  - Phosphoprotein phosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: A phosphoprotein + H2O = a protein + phosphate
phosphoprotein
 + H(2)O
 = protein
 + phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     PTW/PP1 phosphatase complex   14 terms 
  Biological process     cell cycle   6 terms 
  Biochemical function     protein binding     6 terms  

 

 
    Added reference    
 
 
DOI no: 10.1074/jbc.M703472200 J Biol Chem 282:28874-28883 (2007)
PubMed id: 17636256  
 
 
Structural basis for regulation of protein phosphatase 1 by inhibitor-2.
T.D.Hurley, J.Yang, L.Zhang, K.D.Goodwin, Q.Zou, M.Cortese, A.K.Dunker, A.A.Depaoli-Roach.
 
  ABSTRACT  
 
The functional specificity of type 1 protein phosphatases (PP1) depends on the associated regulatory/targeting and inhibitory subunits. To gain insights into the mechanism of PP1 regulation by inhibitor-2, an ancient and intrinsically disordered regulator, we solved the crystal structure of the complex to 2.5A resolution. Our studies show that, when complexed with PP1c, I-2 acquires three regions of order: site 1, residues 12-17, binds adjacent to a region recognized by many PP1 regulators; site 2, amino acids 44-56, interacts along the RVXF binding groove through an unsuspected sequence, KSQKW; and site 3, residues 130-169, forms alpha-helical regions that lie across the substrate-binding cleft. Specifically, residues 148-151 interact at the catalytic center, displacing essential metal ions, accounting for both rapid inhibition and slower inactivation of PP1c. Thus, our structure provides novel insights into the mechanism of PP1 inhibition and subsequent reactivation, has broad implications for the physiological regulation of PP1, and highlights common inhibitory interactions among phosphoprotein phosphatase family members.
 
  Selected figure(s)  
 
Figure 2.
FIGURE 2. Observed structure of the PP1c ·I-2 complex. a, the ribbon structure of PP1c is represented in blue, and that of I-2 is in magenta. Residue numbers indicate the start and stop points for the observed regions of I-2, as well as the last residue observed for PP1c (300). The position of the remaining catalytic manganese ion is indicated (Mn), as is the position of the water molecule (Wat). Omit [A]-weighted electron density contoured at one standard deviation for residues 12-17 of I-2 (b), residues 44-56 of I-2 (c), and residues 145-155 of I-2 (d). Figs. 2, 4(b-d), and 5, 6 and 7 were produced using SPDB-Viewer (54) and POV-Ray for Windows (55). 		Figure 6.
FIGURE 6. Common and unique interactions across the surface of PP1c. a, structure alignment of residues from R[GL] (green), MYPT1 (blue), and I-2 (red) that bind along the RVXF binding groove. The identity of the residues at each position is indicated using the single-amino acid code in the appropriate color. b, structure alignment of the PP1c ·MYPT1 (Protein Data Bank code 1wao, blue and red, respectively) complex to the PP1c ·I-2 complex (cyan and magenta, respectively).
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2007, 282, 28874-28883) copyright 2007.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21222654 G.W.Templeton, M.Nimick, N.Morrice, D.Campbell, M.Goudreault, A.C.Gingras, A.Takemiya, K.Shimazaki, and G.B.Moorhead (2011).
Identification and characterization of AtI-2, an Arabidopsis homologue of an ancient protein phosphatase 1 (PP1) regulatory subunit.
  Biochem J, 435, 73-83.  
21049125 V.N.Uversky (2011).
Multitude of binding modes attainable by intrinsically disordered proteins: a portrait gallery of disorder-based complexes.
  Chem Soc Rev, 40, 1623-1634.  
20826336 J.A.Marsh, B.Dancheck, M.J.Ragusa, M.Allaire, J.D.Forman-Kay, and W.Peti (2010).
Structural diversity in free and bound states of intrinsically disordered protein phosphatase 1 regulators.
  Structure, 18, 1094-1103.  
20399103 M.Bollen, W.Peti, M.J.Ragusa, and M.Beullens (2010).
The extended PP1 toolkit: designed to create specificity.
  Trends Biochem Sci, 35, 450-458.  
20305656 M.J.Ragusa, B.Dancheck, D.A.Critton, A.C.Nairn, R.Page, and W.Peti (2010).
Spinophilin directs protein phosphatase 1 specificity by blocking substrate binding sites.
  Nat Struct Mol Biol, 17, 459-464.
PDB codes: 3egg 3egh 3hvq
20826332 V.N.Uversky (2010).
Seven lessons from one IDP structural analysis.
  Structure, 18, 1069-1071.  
19887526 Y.C.Huang, Y.C.Chen, H.J.Tsay, C.L.Chyan, C.Y.Chen, H.B.Huang, and T.H.Lin (2010).
The effect of PKA-phosphorylation on the structure of inhibitor-1 studied by NMR spectroscopy.
  J Biochem, 147, 273-278.  
19389623 A.Hendrickx, M.Beullens, H.Ceulemans, T.Den Abt, A.Van Eynde, E.Nicolaescu, B.Lesage, and M.Bollen (2009).
Docking motif-guided mapping of the interactome of protein phosphatase-1.
  Chem Biol, 16, 365-371.  
19412530 B.Mészáros, I.Simon, and Z.Dosztányi (2009).
Prediction of protein binding regions in disordered proteins.
  PLoS Comput Biol, 5, e1000376.  
19285938 D.M.Virshup, and S.Shenolikar (2009).
From promiscuity to precision: protein phosphatases get a makeover.
  Mol Cell, 33, 537-545.  
19846560 M.Eto (2009).
Regulation of cellular protein phosphatase-1 (PP1) by phosphorylation of the CPI-17 family, C-kinase-activated PP1 inhibitors.
  J Biol Chem, 284, 35273-35277.  
19273294 P.Nicolaou, and E.G.Kranias (2009).
Role of PP1 in the regulation of Ca cycling in cardiac physiology and pathophysiology.
  Front Biosci, 14, 3571-3585.  
19332797 S.Martínez-Martínez, L.Genescà, A.Rodríguez, A.Raya, E.Salichs, F.Were, M.D.López-Maderuelo, J.M.Redondo, and S.de la Luna (2009).
The RCAN carboxyl end mediates calcineurin docking-dependent inhibition via a site that dictates binding to substrates and regulators.
  Proc Natl Acad Sci U S A, 106, 6117-6122.  
19273587 S.Mehta, H.Li, P.G.Hogan, and K.W.Cunningham (2009).
Domain architecture of the regulators of calcineurin (RCANs) and identification of a divergent RCAN in yeast.
  Mol Cell Biol, 29, 2777-2793.  
18954090 B.Dancheck, A.C.Nairn, and W.Peti (2008).
Detailed structural characterization of unbound protein phosphatase 1 inhibitors.
  Biochemistry, 47, 12346-12356.  
18394161 B.Suchanova, and R.Tuma (2008).
Folding and assembly of large macromolecular complexes monitored by hydrogen-deuterium exchange and mass spectrometry.
  Microb Cell Fact, 7, 12.  
19000314 G.B.Moorhead, L.Trinkle-Mulcahy, M.Nimick, V.De Wever, D.G.Campbell, R.Gourlay, Y.W.Lam, and A.I.Lamond (2008).
Displacement affinity chromatography of protein phosphatase one (PP1) complexes.
  BMC Biochem, 9, 28.  
18951879 L.Zhang, Z.Qi, Y.Gao, and E.Y.Lee (2008).
Identification of the interaction sites of Inhibitor-3 for protein phosphatase-1.
  Biochem Biophys Res Commun, 377, 710-713.  
18619997 M.S.Cortese, V.N.Uversky, and A.K.Dunker (2008).
Intrinsic disorder in scaffold proteins: getting more from less.
  Prog Biophys Mol Biol, 98, 85.  
19020623 R.A.Hanna, R.L.Campbell, and P.L.Davies (2008).
Calcium-bound structure of calpain and its mechanism of inhibition by calpastatin.
  Nature, 456, 409-412.
PDB code: 3bow
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.