PDBsum entry 2ixm

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Hydrolase activator PDB id
Protein chain
300 a.a. *
Waters ×242
* Residue conservation analysis
PDB id:
Name: Hydrolase activator
Title: Structure of human ptpa
Structure: Serine/threonine-protein phosphatase 2a regulatory subunit b'. Chain: a. Fragment: residues 20-322. Synonym: protein phosphatase 2a activator, pp2a, subunit b', pr53 isoform, phosphotyrosyl phosphatase activator, ptpa. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.50Å     R-factor:   0.203     R-free:   0.221
Authors: N.Leulliot,G.Vicentini,J.Jordens,S.Quevillon-Cheruel, M.Schiltz,D.Barford,H.Van Tilbeurgh,J.Goris
Key ref:
N.Leulliot et al. (2006). Crystal structure of the PP2A phosphatase activator: implications for its PP2A-specific PPIase activity. Mol Cell, 23, 413-424. PubMed id: 16885030 DOI: 10.1016/j.molcel.2006.07.008
09-Jul-06     Release date:   11-Jul-06    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q15257  (PTPA_HUMAN) -  Serine/threonine-protein phosphatase 2A activator
358 a.a.
300 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.  - 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!
  Biochemical function     phosphatase activator activity     1 term  


    Added reference    
DOI no: 10.1016/j.molcel.2006.07.008 Mol Cell 23:413-424 (2006)
PubMed id: 16885030  
Crystal structure of the PP2A phosphatase activator: implications for its PP2A-specific PPIase activity.
N.Leulliot, G.Vicentini, J.Jordens, S.Quevillon-Cheruel, M.Schiltz, D.Barford, H.van Tilbeurgh, J.Goris.
PTPA, an essential and specific activator of protein phosphatase 2A (PP2A), functions as a peptidyl prolyl isomerase (PPIase). We present here the crystal structures of human PTPA and of the two yeast orthologs (Ypa1 and Ypa2), revealing an all alpha-helical protein fold that is radically different from other PPIases. The protein is organized into two domains separated by a groove lined by highly conserved residues. To understand the molecular mechanism of PTPA activity, Ypa1 was cocrystallized with a proline-containing PPIase peptide substrate. In the complex, the peptide binds at the interface of a peptide-induced dimer interface. Conserved residues of the interdomain groove contribute to the peptide binding site and dimer interface. Structure-guided mutational studies showed that in vivo PTPA activity is influenced by mutations on the surface of the peptide binding pocket, the same mutations that also influenced the in vitro activation of PP2Ai and PPIase activity.
  Selected figure(s)  
Figure 2.
Figure 2. Structure of PTPA Homologs
(A) Topology of the PTPA fold. The bimodular structure is formed by domain A (helices 3–7) and domain B (helices 8–13).
(B) Structural superposition of hPTPAΔ (blue), Ypa1Δ (green), and Ypa2Δ (red), in about the same orientation as (C).
(C) Stereo cartoon representation of the Ypa1Δ monomer. The helices are colored with the same color code as (A).
(D) Surface representation of the Ypa1Δ monomer. The surface is color coded in increasing shades of red representing conservation of the surface residue. The left panel has the same orientation as (C), whereas in the right panel, the Ypa1Δ monomer is rotated over 180°.
Figure 4.
Figure 4. Structure of Ypa1Δ in Complex with the PPIase Substrate suc-AAPK-pNa
(A) Binding of the suc-AAPK-pNa peptide involves dimerization of Ypa1Δ. One monomer has the same color code as Figures 2A and 2B, the other is represented in surface colored as in Figure 2D. The F[o] − F[c] electron density contoured at 3σ is shown for the PPIase peptides.
(B) Stereo view of the peptide binding pocket. The two monomers are colored red and blue. The residues of the protein in proximity to the peptide are labeled. The residues labeled in red correspond to the region deleted in the inactive mutant from O. cuniculus.
(C) Close-up view of the stacking interaction of Trp202 and the peptide proline. Peptide residues are labeled in bold.
  The above figures are reprinted by permission from Cell Press: Mol Cell (2006, 23, 413-424) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20382998 M.Schiltz, and G.Bricogne (2010).
'Broken symmetries' in macromolecular crystallography: phasing from unmerged data.
  Acta Crystallogr D Biol Crystallogr, 66, 447-457.  
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.  
18291659 V.Janssens, S.Longin, and J.Goris (2008).
PP2A holoenzyme assembly: in cauda venenum (the sting is in the tail).
  Trends Biochem Sci, 33, 113-121.  
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.  
17876319 K.P.Lu, G.Finn, T.H.Lee, and L.K.Nicholson (2007).
Prolyl cis-trans isomerization as a molecular timer.
  Nat Chem Biol, 3, 619-629.  
17333320 S.Azam, E.Drobetsky, and D.Ramotar (2007).
Overexpression of the cis/trans isomerase PTPA triggers caspase 3-dependent apoptosis.
  Apoptosis, 12, 1243-1255.  
17391644 S.J.Yoo, J.M.Boylan, D.L.Brautigan, and P.A.Gruppuso (2007).
Subunit composition and developmental regulation of hepatic protein phosphatase 2A (PP2A).
  Arch Biochem Biophys, 461, 186-193.  
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.