PDBsum entry 1nmw

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Isomerase PDB id
Protein chain
114 a.a. *
* Residue conservation analysis
PDB id:
Name: Isomerase
Title: Solution structure of the ppiase domain of human pin1
Structure: Peptidyl-prolyl cis-trans isomerase nima-interact chain: a. Fragment: ppiase domain (residues 50-163). Synonym: rotamase pin1, ppiase pin1. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: pin1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
NMR struc: 10 models
Authors: E.Bayer,S.Goettsch,J.W.Mueller,B.Griewel,E.Guiberman,L.Mayr,
Key ref:
E.Bayer et al. (2003). Structural analysis of the mitotic regulator hPin1 in solution: insights into domain architecture and substrate binding. J Biol Chem, 278, 26183-26193. PubMed id: 12721297 DOI: 10.1074/jbc.M300721200
12-Jan-03     Release date:   15-Jul-03    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q13526  (PIN1_HUMAN) -  Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1
163 a.a.
114 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!
  Biochemical function     isomerase activity     1 term  


    Added reference    
DOI no: 10.1074/jbc.M300721200 J Biol Chem 278:26183-26193 (2003)
PubMed id: 12721297  
Structural analysis of the mitotic regulator hPin1 in solution: insights into domain architecture and substrate binding.
E.Bayer, S.Goettsch, J.W.Mueller, B.Griewel, E.Guiberman, L.M.Mayr, P.Bayer.
The peptidyl-prolyl cis/trans isomerase hPin1 is a phosphorylation-dependent regulatory enzyme whose substrates are proteins involved in regulation of cell cycle, transcription, Alzheimer's disease, and cancer pathogenesis. We have determined the solution structure of the two domain protein hPin1-(1-163) and its separately expressed PPIase domain (50-163) (hPin1PPIase) with an root mean square deviation of <0.5 A over backbone atoms using NMR. Domain organization of hPin1 differs from that observed in structures solved by x-ray crystallography. Whereas PPIase and WW domain are tightly packed onto each other and share a common binding interface in crystals, our NMR-based data revealed only weak interaction of both domains at their interface in solution. Interaction between the two domains of full-length hPin1 is absent when the protein is dissected into the catalytic and the WW domain. It indicates that the flexible linker, connecting both domains, promotes binding. By evaluation of NOESY spectra we can show that the alpha1/beta1 loop, which was proposed to undergo a large conformational rearrangement in the absence of sulfate and an Ala-Pro peptide, remained in the closed conformation under these conditions. Dissociation constants of 0.4 and 2.0 mm for sulfate and phosphate ions were measured at 12 degrees C by fluorescence spectroscopy. Binding of sulfate prevents hPin1 aggregation and changes surface charges across the active center and around the reactive and catalytically essential Cys113. In the absence of sulfate and/or reducing agent this residue seems to promote aggregation, as observed in hPin1 solutions in vitro.
  Selected figure(s)  
Figure 4.
FIG. 4. Structural comparison of solution and crystal structures of the PPIase domain of hPin1. Top, the C[ ]trace of the PPIase domain of the solution structure (red) is superimposed with the crystal structure solved by Verdecia et al. (13) (blue) (A) and Ranganathan et al. (14) (cyan) (B). Bottom, differences in angles between the solution structure and crystal structures from A and B are plotted.
Figure 9.
FIG. 9. GRASP surface representation of hPin1[PPIase]. Molecular surfaces are colored according to electric potential. Blue colors represent positive charges, red colors are negative charges, and neutral areas are gray. Calculation of electric potential was done, including the potential of the complexed sulfate ion (A) or excluding it (B). Indicated are charged residues and amino acids of the active center.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 26183-26193) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
19681904 M.R.Kim, H.K.Choi, K.B.Cho, H.S.Kim, and K.W.Kang (2009).
Involvement of Pin1 induction in epithelial-mesenchymal transition of tamoxifen-resistant breast cancer cells.
  Cancer Sci, 100, 1834-1841.  
19309529 O.Heikkinen, R.Seppala, H.Tossavainen, S.Heikkinen, H.Koskela, P.Permi, and I.Kilpeläinen (2009).
Solution structure of the parvulin-type PPIase domain of Staphylococcus aureus PrsA--implications for the catalytic mechanism of parvulins.
  BMC Struct Biol, 9, 17.
PDB code: 2jzv
  19787094 J.W.Mueller, and P.Bayer (2008).
Small family with key contacts: par14 and par17 parvulin proteins, relatives of pin1, now emerge in biomedical research.
  Perspect Medicin Chem, 2, 11-20.  
18635547 P.Rudrabhatla, Y.L.Zheng, N.D.Amin, S.Kesavapany, W.Albers, and H.C.Pant (2008).
Pin1-dependent prolyl isomerization modulates the stress-induced phosphorylation of high molecular weight neurofilament protein.
  J Biol Chem, 283, 26737-26747.  
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.  
17875217 D.Kessler, P.Papatheodorou, T.Stratmann, E.A.Dian, C.Hartmann-Fatu, J.Rassow, P.Bayer, and J.W.Mueller (2007).
The DNA binding parvulin Par17 is targeted to the mitochondrial matrix by a recently evolved prepeptide uniquely present in Hominidae.
  BMC Biol, 5, 37.  
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.  
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.  
17316687 W.Labeikovsky, E.Z.Eisenmesser, D.A.Bosco, and D.Kern (2007).
Structure and dynamics of pin1 during catalysis by NMR.
  J Mol Biol, 367, 1370-1381.  
16648162 F.Cecconi, C.Guardiani, and R.Livi (2006).
Testing simplified proteins models of the hPin1 WW domain.
  Biophys J, 91, 694-704.  
16522211 J.W.Mueller, D.Kessler, D.Neumann, T.Stratmann, P.Papatheodorou, C.Hartmann-Fatu, and P.Bayer (2006).
Characterization of novel elongated Parvulin isoforms that are ubiquitously expressed in human tissues and originate from alternative transcription initiation.
  BMC Mol Biol, 7, 9.  
16807295 M.Jäger, Y.Zhang, J.Bieschke, H.Nguyen, M.Dendle, M.E.Bowman, J.P.Noel, M.Gruebele, and J.W.Kelly (2006).
Structure-function-folding relationship in a WW domain.
  Proc Natl Acad Sci U S A, 103, 10648-10653.
PDB codes: 1zcn 2f21
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.