PDBsum entry 1i8g

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Hydrolase/isomerase PDB id
Protein chain
39 a.a. *
* Residue conservation analysis
PDB id:
Name: Hydrolase/isomerase
Title: Solution structure of pin1 ww domain complexed with cdc25 phosphothreonine peptide
Structure: M-phase inducer phosphatase 3. Chain: a. Fragment: residues 63-72. Engineered: yes. Peptidyl-prolyl cis-trans isomerase nima- interacting 1. Chain: b. Fragment: ww domain (residues 6-44). Engineered: yes
Source: Synthetic: yes. Other_details: the ligand phosphopeptide was synthesized from rink amide resin using the fmoc strategy and activation by hbtu and hobt in a 431a peptide synthesizer. The sequence of the peptide is naturally found in xenopus laevis (african clawed frog).. Other_details: the pin1 ww domain was obtained by peptide synthesis using the boc-benzyl strategy and the hbtu in situ activation protocol on an applied 430a peptide
NMR struc: 10 models
Authors: R.Wintjens,J.-M.Wieruszeski,H.Drobecq,G.Lippens,I.Landrieu
Key ref:
R.Wintjens et al. (2001). 1H NMR study on the binding of Pin1 Trp-Trp domain with phosphothreonine peptides. J Biol Chem, 276, 25150-25156. PubMed id: 11313338 DOI: 10.1074/jbc.M010327200
14-Mar-01     Release date:   18-Jul-01    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q13526  (PIN1_HUMAN) -  Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1
163 a.a.
39 a.a.
Key:    PfamA domain  Secondary structure

 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


    Added reference    
DOI no: 10.1074/jbc.M010327200 J Biol Chem 276:25150-25156 (2001)
PubMed id: 11313338  
1H NMR study on the binding of Pin1 Trp-Trp domain with phosphothreonine peptides.
R.Wintjens, J.M.Wieruszeski, H.Drobecq, P.Rousselot-Pailley, L.Buée, G.Lippens, I.Landrieu.
The recent crystal structure of Pin1 protein bound to a doubly phosphorylated peptide from the C-terminal domain of RNA polymerase II revealed that binding interactions between Pin1 and its substrate take place through its Trp-Trp (WW) domain at the level of the loop Ser(11)-Arg(12) and the aromatic pair Tyr(18)-Trp(29), and showed a trans conformation for both pSer-Pro peptide bonds. However, the orientation of the ligand in the aromatic recognition groove still could be sequence-specific, as previously observed in SH3 domains complexed by peptide ligands or for different class of WW domains (Zarrinpar, A., and Lim, W. A. (2000) Nat. Struct. Biol. 7, 611-613). Because the bound peptide conformation could also differ as observed for peptide ligands bound to the 14-3-3 domain, ligand orientation and conformation for two other biologically relevant monophosphate substrates, one derived from the Cdc25 phosphatase of Xenopus laevis (EQPLpTPVTDL) and another from the human tau protein (KVSVVRpTPPKSPS) in complex with the WW domain are here studied by solution NMR methods. First, the proton resonance perturbations on the WW domain upon complexation with both peptide ligands were determined to be essentially located in the positively charged beta-hairpin Ser(11)-Gly(15) and around the aromatic Trp(29). Dissociation equilibrium constants of 117 and 230 microm for Cdc25 and tau peptides, respectively, were found. Several intermolecular nuclear Overhauser effects between WW domain and substrates were obtained from a ligand-saturated solution and were used to determine the structures of the complexes in solution. We found a similar N to C orientation as the one observed in the crystal complex structure of Pin1 and a trans conformation for the pThr-Pro peptidic bond in both peptide ligands, thereby indicating a unique binding scheme for the Pin1 WW domain to its multiple substrates.
  Selected figure(s)  
Figure 5.
Fig. 5. Stereo view of the overlaid backbone traces of the 20 final conformers of the complex between the Pin1 WW domain and a Cdc25 peptide ligand. Superposition was done on residues (4-32) of the WW domain.
Figure 6.
Fig. 6. Ribbon drawing of the NMR reference structure of the complex between Pin1 WW domain (in light blue) and phosphopeptide ligand (in red), in comparison with the orientation of the CTD peptide (in violet) from the crystallographic model of the complex (13). The image was obtained by backbone superimposition of WW domains from our NMR complex and from the CTD peptide/Pin1 complex (13). Only the WW domain from this study and both phosphopeptide ligands are represented. Side chains implicated into the binding interface are labeled (in white for the WW domain residues and yellow for the ligand residues) and depicted in detail, as well as the amino acid pair Trp6-Pro32 of the WW domain. N atoms are blue and P atoms are violet. C atoms are green in the WW domain and orange in the tau ligand.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2001, 276, 25150-25156) copyright 2001.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20586101 M.Popovic, J.Bella, V.Zlatev, V.Hodnik, G.Anderluh, P.N.Barlow, A.Pintar, and S.Pongor (2011).
The interaction of Jagged-1 cytoplasmic tail with afadin PDZ domain is local, folding-independent, and tuned by phosphorylation.
  J Mol Recognit, 24, 245-253.  
21152000 F.Morcos, S.Chatterjee, C.L.McClendon, P.R.Brenner, R.López-Rendón, J.Zintsmaster, M.Ercsey-Ravasz, C.R.Sweet, M.P.Jacobson, J.W.Peng, and J.A.Izaguirre (2010).
Modeling conformational ensembles of slow functional motions in Pin1-WW.
  PLoS Comput Biol, 6, e1001015.  
19291099 B.Wu, M.F.Rega, J.Wei, H.Yuan, R.Dahl, Z.Zhang, and M.Pellecchia (2009).
Discovery and binding studies on a series of novel Pin1 ligands.
  Chem Biol Drug Des, 73, 369-379.  
19639385 J.W.Peng, B.D.Wilson, and A.T.Namanja (2009).
Mapping the dynamics of ligand reorganization via 13CH3 and 13CH2 relaxation dispersion at natural abundance.
  J Biomol NMR, 45, 171-183.  
19401603 K.Yotsumoto, T.Saito, A.Asada, T.Oikawa, T.Kimura, C.Uchida, K.Ishiguro, T.Uchida, M.Hasegawa, and S.Hisanaga (2009).
Effect of Pin1 or microtubule binding on dephosphorylation of FTDP-17 mutant Tau.
  J Biol Chem, 284, 16840-16847.  
18834120 J.S.Zintsmaster, B.D.Wilson, and J.W.Peng (2008).
Dynamics of ligand binding from 13C NMR relaxation dispersion at natural abundance.
  J Am Chem Soc, 130, 14060-14061.  
17355867 A.T.Namanja, T.Peng, J.S.Zintsmaster, A.C.Elson, M.G.Shakour, and J.W.Peng (2007).
Substrate recognition reduces side-chain flexibility for conserved hydrophobic residues in human Pin1.
  Structure, 15, 313-327.  
17892493 G.Lippens, I.Landrieu, and C.Smet (2007).
Molecular mechanisms of the phospho-dependent prolyl cis/trans isomerase Pin1.
  FEBS J, 274, 5211-5222.  
17878917 K.P.Lu, and X.Z.Zhou (2007).
The prolyl isomerase PIN1: a pivotal new twist in phosphorylation signalling and disease.
  Nat Rev Mol Cell Biol, 8, 904-916.  
17571276 M.Hamdane, and L.Buée (2007).
The complex p25/Cdk5 kinase in neurofibrillary degeneration and neuronal death: the missing link to cell cycle.
  Biotechnol J, 2, 967-977.  
17328589 P.Brenner, C.R.Sweet, D.VonHandorf, and J.A.Izaguirre (2007).
Accelerating the replica exchange method through an efficient all-pairs exchange.
  J Chem Phys, 126, 074103.  
17626162 S.Kesavapany, V.Patel, Y.L.Zheng, T.K.Pareek, M.Bjelogrlic, W.Albers, N.Amin, H.Jaffe, J.S.Gutkind, M.J.Strong, P.Grant, and H.C.Pant (2007).
Inhibition of Pin1 reduces glutamate-induced perikaryal accumulation of phosphorylated neurofilament-H in neurons.
  Mol Biol Cell, 18, 3645-3655.  
17334375 T.Peng, J.S.Zintsmaster, A.T.Namanja, and J.W.Peng (2007).
Sequence-specific dynamics modulate recognition specificity in WW domains.
  Nat Struct Mol Biol, 14, 325-331.  
16652378 K.P.Lu, F.Suizu, X.Z.Zhou, G.Finn, P.Lam, and G.Wulf (2006).
Targeting carcinogenesis: a role for the prolyl isomerase Pin1?
  Mol Carcinog, 45, 397-402.  
16554819 L.Pastorino, A.Sun, P.J.Lu, X.Z.Zhou, M.Balastik, G.Finn, G.Wulf, J.Lim, S.H.Li, X.Li, W.Xia, L.K.Nicholson, and K.P.Lu (2006).
The prolyl isomerase Pin1 regulates amyloid precursor protein processing and amyloid-beta production.
  Nature, 440, 528-534.  
16274748 R.L.Neve, and D.L.McPhie (2006).
The cell cycle as a therapeutic target for Alzheimer's disease.
  Pharmacol Ther, 111, 99.  
16302169 X.J.Wang, and F.A.Etzkorn (2006).
Peptidyl-prolyl isomerase inhibitors.
  Biopolymers, 84, 125-146.  
16294313 K.N.Barnouin, S.R.Hart, A.J.Thompson, M.Okuyama, M.Waterfield, and R.Cramer (2005).
Enhanced phosphopeptide isolation by Fe(III)-IMAC using 1,1,1,3,3,3-hexafluoroisopropanol.
  Proteomics, 5, 4376-4388.  
16177782 M.Socolich, S.W.Lockless, W.P.Russ, H.Lee, K.H.Gardner, and R.Ranganathan (2005).
Evolutionary information for specifying a protein fold.
  Nature, 437, 512-518.
PDB code: 1ymz
15044739 C.M.Santiveri, J.Santoro, M.Rico, and M.A.Jiménez (2004).
Factors involved in the stability of isolated beta-sheets: Turn sequence, beta-sheet twisting, and hydrophobic surface burial.
  Protein Sci, 13, 1134-1147.  
14695515 G.Lippens, J.M.Wieruszeski, A.Leroy, C.Smet, A.Sillen, L.Buée, and I.Landrieu (2004).
Proline-directed random-coil chemical shift values as a tool for the NMR assignment of the tau phosphorylation sites.
  Chembiochem, 5, 73-78.  
12471608 T.Wang, and R.C.Wade (2003).
Implicit solvent models for flexible protein-protein docking by molecular dynamics simulation.
  Proteins, 50, 158-169.  
11978535 K.P.Lu, Y.C.Liou, and X.Z.Zhou (2002).
Pinning down proline-directed phosphorylation signaling.
  Trends Cell Biol, 12, 164-172.  
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.