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PDBsum entry 3kad

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protein ligands links
Isomerase PDB id
3kad
Jmol
Contents
Protein chain
145 a.a. *
Ligands
4C0
12P
Waters ×165
* Residue conservation analysis
PDB id:
3kad
Name: Isomerase
Title: Structure-guided design of alpha-amino acid-derived pin1 inhibitors
Structure: Peptidyl-prolyl cis-trans isomerase nima- interacting 1. Chain: a. Synonym: rotamase pin1, ppiase pin1. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: pin1. Expressed in: escherichia coli. Expression_system_taxid: 469008.
Resolution:
1.95Å     R-factor:   0.191     R-free:   0.248
Authors: L.M.Baker,P.Dokurno,D.A.Robinson,A.E.Surgenor,J.B.Murray, A.J.Potter,J.D.Moore
Key ref: A.J.Potter et al. (2010). Structure-guided design of alpha-amino acid-derived Pin1 inhibitors. Bioorg Med Chem Lett, 20, 586-590. PubMed id: 19969456 DOI: 10.1016/j.bmcl.2009.11.090
Date:
19-Oct-09     Release date:   22-Dec-09    
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 2 residue positions (black crosses)

 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     negative regulation of cell motility   15 terms 
  Biochemical function     protein binding     7 terms  

 

 
    Added reference    
 
 
DOI no: 10.1016/j.bmcl.2009.11.090 Bioorg Med Chem Lett 20:586-590 (2010)
PubMed id: 19969456  
 
 
Structure-guided design of alpha-amino acid-derived Pin1 inhibitors.
A.J.Potter, S.Ray, L.Gueritz, C.L.Nunns, C.J.Bryant, S.F.Scrace, N.Matassova, L.Baker, P.Dokurno, D.A.Robinson, A.E.Surgenor, B.Davis, J.B.Murray, C.M.Richardson, J.D.Moore.
 
  ABSTRACT  
 
The peptidyl prolyl cis/trans isomerase Pin1 is a promising molecular target for anti-cancer therapeutics. Here we report the structure-guided evolution of an indole 2-carboxylic acid fragment hit into a series of alpha-benzimidazolyl-substituted amino acids. Examples inhibited Pin1 activity with IC(50) <100nM, but were inactive on cells. Replacement of the benzimidazole ring with a naphthyl group resulted in a 10-50-fold loss in ligand potency, but these examples downregulated biomarkers of Pin1 activity and blocked proliferation of PC3 cells.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21504850 L.Zhu, J.Jin, C.Liu, C.Zhang, Y.Sun, Y.Guo, D.Fu, X.Chen, and B.Xu (2011).
Synthesis and biological evaluation of novel quinazoline-derived human Pin1 inhibitors.
  Bioorg Med Chem, 19, 2797-2807.  
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.