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PDBsum entry 2q5a

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protein ligands links
Isomerase/isomerase inhibitor PDB id
2q5a
Jmol
Contents
Protein chain
145 a.a. *
Ligands
PHE-TPO-YCP-NAL-
GLN-NH2
16P
Waters ×167
* Residue conservation analysis
PDB id:
2q5a
Name: Isomerase/isomerase inhibitor
Title: Human pin1 bound to l-peptide
Structure: Peptidyl-prolyl cis-trans isomerase nima-interact chain: a. Synonym: rotamase pin1, ppiase pin1. Engineered: yes. Mutation: yes. Five residue peptide. Chain: b. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Strain: hela. Gene: pin1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: synthetic peptide
Resolution:
1.50Å     R-factor:   0.233     R-free:   0.252
Authors: J.P.Noel,Y.Zhang
Key ref: Y.Zhang et al. (2007). Structural basis for high-affinity peptide inhibition of human Pin1. ACS Chem Biol, 2, 320-328. PubMed id: 17518432
Date:
31-May-07     Release date:   26-Jun-07    
Supersedes: 2iti
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q13526  (PIN1_HUMAN) -  Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1
Seq:
Struc:
163 a.a.
145 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.5.2.1.8  - 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     midbody   5 terms 
  Biological process     metabolic process   15 terms 
  Biochemical function     protein binding     7 terms  

 

 
    Added reference    
 
 
ACS Chem Biol 2:320-328 (2007)
PubMed id: 17518432  
 
 
Structural basis for high-affinity peptide inhibition of human Pin1.
Y.Zhang, S.Daum, D.Wildemann, X.Z.Zhou, M.A.Verdecia, M.E.Bowman, C.Lücke, T.Hunter, K.P.Lu, G.Fischer, J.P.Noel.
 
  ABSTRACT  
 
Human Pin1 is a key regulator of cell-cycle progression and plays growth-promoting roles in human cancers. High-affinity inhibitors of Pin1 may provide a unique opportunity for disrupting oncogenic pathways. Here we report two high-resolution X-ray crystal structures of human Pin1 bound to non-natural peptide inhibitors. The structures of the bound high-affinity peptides identify a type-I beta-turn conformation for Pin1 prolyl peptide isomerase domain-peptide binding and an extensive molecular interface for high-affinity recognition. Moreover, these structures suggest chemical elements that may further improve the affinity and pharmacological properties of future peptide-based Pin inhibitors. Finally, an intramolecular hydrogen bond observed in both peptide complexes mimics the cyclic conformation of FK506 and rapamycin. Both FK506 and rapamycin are clinically important inhibitors of other peptidyl-prolyl cis-trans isomerases. This comparative discovery suggests that a cyclic peptide polyketide bridge, like that found in FK506 and rapamycin or a similar linkage, may significantly improve the binding affinity of structure-based Pin1 inhibitors.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20549604 D.Clayton, I.Hanchapola, N.Hausler, S.Unabia, R.A.Lew, R.E.Widdop, A.I.Smith, P.Perlmutter, and M.I.Aguilar (2011).
β-amino acid substitution to investigate the recognition of angiotensin II (AngII) by angiotensin converting enzyme 2 (ACE2).
  J Mol Recognit, 24, 235-244.  
21497122 T.H.Lee, C.H.Chen, F.Suizu, P.Huang, C.Schiene-Fischer, S.Daum, Y.J.Zhang, A.Goate, R.H.Chen, X.Z.Zhou, and K.P.Lu (2011).
Death-associated protein kinase 1 phosphorylates Pin1 and inhibits its prolyl isomerase activity and cellular function.
  Mol Cell, 42, 147-159.  
20102178 G.G.Xu, and F.A.Etzkorn (2010).
Convergent synthesis of alpha-ketoamide inhibitors of Pin1.
  Org Lett, 12, 696-699.  
20574990 K.Hong Lim, C.K.Hsu, and S.Park (2010).
Flow cytometric analysis of genetic FRET detectors containing variable substrate sequences.
  Biotechnol Prog, 26, 1765-1771.  
20180533 T.Liu, Y.Liu, H.Y.Kao, and D.Pei (2010).
Membrane permeable cyclic peptidyl inhibitors against human Peptidylprolyl Isomerase Pin1.
  J Med Chem, 53, 2494-2501.  
19996102 Y.Fujimoto, T.Shiraki, Y.Horiuchi, T.Waku, A.Shigenaga, A.Otaka, T.Ikura, K.Igarashi, S.Aimoto, S.Tate, and K.Morikawa (2010).
Proline cis/trans-isomerase Pin1 regulates peroxisome proliferator-activated receptor gamma activity through the direct binding to the activation function-1 domain.
  J Biol Chem, 285, 3126-3132.  
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.  
19480458 S.Daum, M.Schumann, S.Mathea, T.Aumüller, M.A.Balsley, S.L.Constant, B.F.de Lacroix, F.Kruska, M.Braun, and C.Schiene-Fischer (2009).
Isoform-specific inhibition of cyclophilins.
  Biochemistry, 48, 6268-6277.  
18539601 C.Fila, C.Metz, and P.van der Sluijs (2008).
Juglone inactivates cysteine-rich proteins required for progression through mitosis.
  J Biol Chem, 283, 21714-21724.  
19055796 P.Slama, I.Filippis, and M.Lappe (2008).
Detection of protein catalytic residues at high precision using local network properties.
  BMC Bioinformatics, 9, 517.  
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.  
17935986 S.Zhao, and F.A.Etzkorn (2007).
A phosphorylated prodrug for the inhibition of Pin1.
  Bioorg Med Chem Lett, 17, 6615-6618.  
17912258 T.R.Hupp, and M.Walkinshaw (2007).
Multienzyme assembly of a p53 transcription complex.
  Nat Struct Mol Biol, 14, 885-887.  
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.