PDBsum entry 3i6c

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Isomerase PDB id
Protein chain
113 a.a. *
GIA ×3
Waters ×166
* Residue conservation analysis
PDB id:
Name: Isomerase
Title: Structure-based design of novel pin1 inhibitors (ii)
Structure: Peptidyl-prolyl cis-trans isomerase nima- interacting 1. Chain: a, b. Fragment: unp residues 45-163. 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: 562
1.30Å     R-factor:   0.164     R-free:   0.214
Authors: S.E.Greasley,R.A.Ferre
Key ref: L.Dong et al. (2010). Structure-based design of novel human Pin1 inhibitors (II). Bioorg Med Chem Lett, 20, 2210-2214. PubMed id: 20207139 DOI: 10.1016/j.bmcl.2010.02.033
06-Jul-09     Release date:   21-Apr-10    
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Protein chains
Pfam   ArchSchema ?
Q13526  (PIN1_HUMAN) -  Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1
163 a.a.
113 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.  - 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: 10.1016/j.bmcl.2010.02.033 Bioorg Med Chem Lett 20:2210-2214 (2010)
PubMed id: 20207139  
Structure-based design of novel human Pin1 inhibitors (II).
L.Dong, J.Marakovits, X.Hou, C.Guo, S.Greasley, E.Dagostino, R.Ferre, M.C.Johnson, E.Kraynov, J.Thomson, V.Pathak, B.W.Murray.
Following the discovery of a novel series of phosphate-containing small molecular Pin1 inhibitors, the drug design strategy shifted to replacement of the phosphate group with an isostere with potential better pharmaceutical properties. The initial loss in potency of carboxylate analogs was likely due to weaker charge-charge interactions in the putative phosphate binding pocket and was subsequently recovered by structure-based optimization of ligand-protein interactions in the proline binding site, leading to the discovery of a sub-micromolar non-phosphate small molecular Pin1 inhibitor.

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.  
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