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PDBsum entry 2p6b
Go to PDB code: 
protein ligands metals Protein-protein interface(s) links
Hydrolase/hydrolase regulator PDB id
2p6b

 

 

 

 

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JSmol PyMol  
Contents
Protein chains
14 a.a.
357 a.a. *
146 a.a. *
Ligands
PO4 ×2
Metals
_CA ×8
_ZN ×2
_FE ×2
Waters ×564
* Residue conservation analysis
PDB id:
2p6b
Name: Hydrolase/hydrolase regulator
Title: Crystal structure of human calcineurin in complex with pvivit peptide
Structure: Pvivit 14-mer peptide. Chain: e. Fragment: residues 3-16. Engineered: yes. Calmodulin-dependent calcineurin a subunit alpha isoform. Chain: a, c. Fragment: residues 1-381. Synonym: serine/threonine-protein phosphatase 2b catalytic subunit alpha isoform. Cam-prp catalytic subunit.
Source: Synthetic: yes. Other_details: synthetic peptide. Homo sapiens. Human. Organism_taxid: 9606. Gene: ppp3ca, calna, cna. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Gene: ppp3r1.
Resolution:
2.30Å     R-factor:   0.192     R-free:   0.254
Authors: H.Li,L.Zhang,A.Rao,S.C.Harrison,P.G.Hogan
Key ref:
H.Li et al. (2007). Structure of Calcineurin in Complex with PVIVIT Peptide: Portrait of a Low-affinity Signalling Interaction. J Mol Biol, 369, 1296-1306. PubMed id: 17498738 DOI: 10.1016/j.jmb.2007.04.032
Date:
16-Mar-07     Release date:   05-Jun-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
No UniProt id for this chain
Struc: 14 a.a.
Protein chains
Pfam   ArchSchema ?
Q08209  (PP2BA_HUMAN) -  Protein phosphatase 3 catalytic subunit alpha from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		521 a.a.
357 a.a.
Protein chains
Pfam   ArchSchema ?
P63098  (CANB1_HUMAN) -  Calcineurin subunit B type 1 from Homo sapiens
Seq:
Struc: 		170 a.a.
146 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains A, C: E.C.3.1.3.16  - protein-serine/threonine phosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction:
1. O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + phosphate
2. O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + phosphate
O-phospho-L-seryl-[protein]
 + H2O
 = L-seryl-[protein]
 +
phosphate
Bound ligand (Het Group name = PO4)
corresponds exactly
O-phospho-L-threonyl-[protein]
 + H2O
 = L-threonyl-[protein]
 +
phosphate
Bound ligand (Het Group name = PO4)
corresponds exactly
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    Added reference    
 
 
DOI no: 10.1016/j.jmb.2007.04.032 J Mol Biol 369:1296-1306 (2007)
PubMed id: 17498738  
 
 
Structure of Calcineurin in Complex with PVIVIT Peptide: Portrait of a Low-affinity Signalling Interaction.
H.Li, L.Zhang, A.Rao, S.C.Harrison, P.G.Hogan.
 
  ABSTRACT  
 
The protein phosphatase calcineurin recognizes a wide assortment of substrates and controls diverse developmental and physiological pathways in eukaryotic cells. Dephosphorylation of the transcription factor NFAT and certain other calcineurin substrates depends on docking of calcineurin at a PxIxIT consensus site. We describe here the structural basis for recognition of the PxIxIT sequence by calcineurin. We demonstrate that the high-affinity peptide ligand PVIVIT adds as a beta-strand to the edge of a beta-sheet of calcineurin; that short peptide segments containing the PxIxIT consensus sequence suffice for calcineurin-substrate docking; and that sequence variations within the PxIxIT core modulate the K(d) of the interaction within the physiological range 1 muM to 1 mM. Calcineurin can adapt to a wide variety of substrates, because recognition requires only a PxIxIT sequence and because variation within the core PxIxIT sequence can fine-tune the affinity to match the physiological signalling requirements of individual substrates.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Structure of human calcineurin in complex with 14mer PVIVIT peptide. (a) Ribbon diagram of PVIVIT (red) sandwiched between two calcineurin heterodimers in the asymmetric unit. CNA molecule A is colored light blue, and its associated CNB, light green. CNA molecule C is colored dark blue, and its associated CNB, purple. (b) Backbone hydrogen bonds connecting PVIVIT peptide to β-sheets of the two CNA molecules. (c) Schematic diagram of (b) depicting the position and register of the peptide with respect to β-strands 14 of the two CNA molecules. Residues numbered in boldface project toward the viewer.
Figure 3.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2007, 369, 1296-1306) copyright 2007.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22343722 H.Li, M.D.Pink, J.G.Murphy, A.Stein, M.L.Dell'Acqua, and P.G.Hogan (2012).
Balanced interactions of calcineurin with AKAP79 regulate Ca2+-calcineurin-NFAT signaling.
  Nat Struct Mol Biol, 19, 337-345.
PDB code: 3ll8
21115349 H.Li, A.Rao, and P.G.Hogan (2011).
Interaction of calcineurin with substrates and targeting proteins.
  Trends Cell Biol, 21, 91.  
21464287 M.G.Gold, F.Stengel, P.J.Nygren, C.R.Weisbrod, J.E.Bruce, C.V.Robinson, D.Barford, and J.D.Scott (2011).
Architecture and dynamics of an A-kinase anchoring protein 79 (AKAP79) signaling complex.
  Proc Natl Acad Sci U S A, 108, 6426-6431.  
20435698 D.Fraga, I.M.Sehring, R.Kissmehl, M.Reiss, R.Gaines, R.Hinrichsen, and H.Plattner (2010).
Protein phosphatase 2B (PP2B, calcineurin) in Paramecium: partial characterization reveals that two members of the unusually large catalytic subunit family have distinct roles in calcium-dependent processes.
  Eukaryot Cell, 9, 1049-1063.  
19285944 A.Rodríguez, J.Roy, S.Martínez-Martínez, M.D.López-Maderuelo, P.Niño-Moreno, L.Ortí, D.Pantoja-Uceda, A.Pineda-Lucena, M.S.Cyert, and J.M.Redondo (2009).
A conserved docking surface on calcineurin mediates interaction with substrates and immunosuppressants.
  Mol Cell, 33, 616-626.  
19290928 J.O.Liu (2009).
Calmodulin-dependent phosphatase, kinases, and transcriptional corepressors involved in T-cell activation.
  Immunol Rev, 228, 184-198.  
19189965 M.C.Mulero, A.Aubareda, M.Orzáez, J.Messeguer, E.Serrano-Candelas, S.Martínez-Hoyer, A.Messeguer, E.Pérez-Payá, and M.Pérez-Riba (2009).
Inhibiting the calcineurin-NFAT (nuclear factor of activated T cells) signaling pathway with a regulator of calcineurin-derived peptide without affecting general calcineurin phosphatase activity.
  J Biol Chem, 284, 9394-9401.  
19351896 M.R.Müller, Y.Sasaki, I.Stevanovic, E.D.Lamperti, S.Ghosh, S.Sharma, C.Gelinas, D.J.Rossi, M.E.Pipkin, K.Rajewsky, P.G.Hogan, and A.Rao (2009).
Requirement for balanced Ca/NFAT signaling in hematopoietic and embryonic development.
  Proc Natl Acad Sci U S A, 106, 7034-7039.  
19860902 M.Sieber, and R.Baumgrass (2009).
Novel inhibitors of the calcineurin/NFATc hub - alternatives to CsA and FK506?
  Cell Commun Signal, 7, 25.  
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.  
19879837 Y.Shi (2009).
Serine/threonine phosphatases: mechanism through structure.
  Cell, 139, 468-484.  
18397886 G.Czirják, D.Vuity, and P.Enyedi (2008).
Phosphorylation-dependent binding of 14-3-3 proteins controls TRESK regulation.
  J Biol Chem, 283, 15672-15680.  
18384083 Q.Ye, H.Wang, J.Zheng, Q.Wei, and Z.Jia (2008).
The complex structure of calmodulin bound to a calcineurin peptide.
  Proteins, 73, 19-27.
PDB code: 2r28
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.

 

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