PDBsum entry 2hv6

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protein metals Protein-protein interface(s) links
Unknown function PDB id
Protein chain
301 a.a. *
Waters ×205
* Residue conservation analysis
PDB id:
Name: Unknown function
Title: Crystal structure of the phosphotyrosyl phosphatase activator
Structure: Protein phosphatase 2a, regulatory subunit b. Chain: a, b. Synonym: pr 53. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ppp2r4. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
1.90Å     R-factor:   0.183     R-free:   0.239
Authors: Y.Chao,P.D.Jeffrey,Y.Shi
Key ref:
Y.Chao et al. (2006). Structure and mechanism of the phosphotyrosyl phosphatase activator. Mol Cell, 23, 535-546. PubMed id: 16916641 DOI: 10.1016/j.molcel.2006.07.027
27-Jul-06     Release date:   22-Aug-06    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q15257  (PTPA_HUMAN) -  Serine/threonine-protein phosphatase 2A activator
358 a.a.
301 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Peptidylprolyl isomerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Peptidylproline (omega=180) = peptidylproline (omega=0)
Peptidylproline (omega=180)
= peptidylproline (omega=0)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     protein phosphatase type 2A complex   6 terms 
  Biological process     protein folding   10 terms 
  Biochemical function     nucleotide binding     12 terms  


    Added reference    
DOI no: 10.1016/j.molcel.2006.07.027 Mol Cell 23:535-546 (2006)
PubMed id: 16916641  
Structure and mechanism of the phosphotyrosyl phosphatase activator.
Y.Chao, Y.Xing, Y.Chen, Y.Xu, Z.Lin, Z.Li, P.D.Jeffrey, J.B.Stock, Y.Shi.
Phosphotyrosyl phosphatase activator (PTPA), also known as PP2A phosphatase activator, is a conserved protein from yeast to human. Here we report the 1.9 A crystal structure of human PTPA, which reveals a previously unreported fold consisting of three subdomains: core, lid, and linker. Structural analysis uncovers a highly conserved surface patch, which borders the three subdomains, and an associated deep pocket located between the core and the linker subdomains. The conserved surface patch and the deep pocket are responsible for binding to PP2A and ATP, respectively. PTPA and PP2A A-C dimer together constitute a composite ATPase. PTPA binding to PP2A results in a dramatic alteration of substrate specificity, with enhanced phosphotyrosine phosphatase activity and decreased phosphoserine phosphatase activity. This function of PTPA strictly depends on the composite ATPase activity. These observations reveal significant insights into the function and mechanism of PTPA and have important ramifications for understanding PP2A function.
  Selected figure(s)  
Figure 3.
Figure 3. Identification of Functional Surface Regions in PTPA
Figure 4.
Figure 4. Identification of the PP2A Binding Surface on the Structure of PTPA
  The above figures are reprinted by permission from Cell Press: Mol Cell (2006, 23, 535-546) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21292165 V.Stanevich, L.Jiang, K.A.Satyshur, Y.Li, P.D.Jeffrey, Z.Li, P.Menden, M.F.Semmelhack, and Y.Xing (2011).
The structural basis for tight control of PP2A methylation and function by LCMT-1.
  Mol Cell, 41, 331-342.
PDB code: 3p71
19156129 T.Glatter, A.Wepf, R.Aebersold, and M.Gstaiger (2009).
An integrated workflow for charting the human interaction proteome: insights into the PP2A system.
  Mol Syst Biol, 5, 237.  
19277525 Y.Shi (2009).
Assembly and structure of protein phosphatase 2A.
  Sci China C Life Sci, 52, 135-146.  
19879837 Y.Shi (2009).
Serine/threonine phosphatases: mechanism through structure.
  Cell, 139, 468-484.  
19747079 Z.Li, and J.B.Stock (2009).
Protein carboxyl methylation and the biochemistry of memory.
  Biol Chem, 390, 1087-1096.  
18214640 A.A.Sablina, and W.C.Hahn (2008).
SV40 small T antigen and PP2A phosphatase in cell transformation.
  Cancer Metastasis Rev, 27, 137-146.  
17803193 D.L.Lizotte, J.J.Blakeslee, A.Siryaporn, J.T.Heath, and A.DeLong (2008).
A PP2A active site mutant impedes growth and causes misregulation of native catalytic subunit expression.
  J Cell Biochem, 103, 1309-1325.  
18596935 S.Ortega-Gutiérrez, D.Leung, S.Ficarro, E.C.Peters, and B.F.Cravatt (2008).
Targeted disruption of the PME-1 gene causes loss of demethylated PP2A and perinatal lethality in mice.
  PLoS ONE, 3, e2486.  
18922469 Y.Xu, Y.Chen, P.Zhang, P.D.Jeffrey, and Y.Shi (2008).
Structure of a protein phosphatase 2A holoenzyme: insights into B55-mediated Tau dephosphorylation.
  Mol Cell, 31, 873-885.
PDB code: 3dw8
17550305 H.Hombauer, D.Weismann, I.Mudrak, C.Stanzel, T.Fellner, D.H.Lackner, and E.Ogris (2007).
Generation of active protein phosphatase 2A is coupled to holoenzyme assembly.
  PLoS Biol, 5, e155.  
17529992 Y.Chen, Y.Xu, Q.Bao, Y.Xing, Z.Li, Z.Lin, J.B.Stock, P.D.Jeffrey, and Y.Shi (2007).
Structural and biochemical insights into the regulation of protein phosphatase 2A by small t antigen of SV40.
  Nat Struct Mol Biol, 14, 527-534.
PDB code: 2pkg
17055435 Y.Xing, Y.Xu, Y.Chen, P.D.Jeffrey, Y.Chao, Z.Lin, Z.Li, S.Strack, J.B.Stock, and Y.Shi (2006).
Structure of protein phosphatase 2A core enzyme bound to tumor-inducing toxins.
  Cell, 127, 341-353.
PDB codes: 2ie3 2ie4
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.