3I6C

Structure-Based Design of Novel PIN1 Inhibitors (II)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.30 Å
  • R-Value Free: 0.214 
  • R-Value Work: 0.164 
  • R-Value Observed: 0.164 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Structure-based design of novel human Pin1 inhibitors (II).

Dong, L.Marakovits, J.Hou, X.Guo, C.Greasley, S.Dagostino, E.Ferre, R.Johnson, M.C.Kraynov, E.Thomson, J.Pathak, V.Murray, B.W.

(2010) Bioorg Med Chem Lett 20: 2210-2214

  • DOI: https://doi.org/10.1016/j.bmcl.2010.02.033
  • Primary Citation of Related Structures:  
    3I6C, 3JYJ

  • PubMed Abstract: 

    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.


  • Organizational Affiliation

    Pfizer Global Research and Development, 10770 Science Center Drive, San Diego, CA 92121, United States.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1
A, B
123Homo sapiensMutation(s): 2 
Gene Names: PIN1
EC: 5.2.1.8
UniProt & NIH Common Fund Data Resources
Find proteins for Q13526 (Homo sapiens)
Explore Q13526 
Go to UniProtKB:  Q13526
PHAROS:  Q13526
GTEx:  ENSG00000127445 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ13526
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
GIA BindingDB:  3I6C Ki: 1.20e+4 (nM) from 1 assay(s)
IC50: 1.20e+4 (nM) from 1 assay(s)
Binding MOAD:  3I6C Ki: 1.20e+4 (nM) from 1 assay(s)
PDBBind:  3I6C Ki: 1.20e+4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.30 Å
  • R-Value Free: 0.214 
  • R-Value Work: 0.164 
  • R-Value Observed: 0.164 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 117.967α = 90
b = 36.648β = 100.99
c = 51.293γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
ARP/wARPmodel building
SHELXL-97refinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-04-21
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2021-10-13
    Changes: Database references, Derived calculations
  • Version 1.3: 2024-02-21
    Changes: Data collection