3IK8

Structure-Based Design of Novel PIN1 Inhibitors (I)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Work: 0.209 
  • R-Value Observed: 0.209 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

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

Guo, C.Hou, X.Dong, L.Dagostino, E.Greasley, S.Ferre, R.Marakovits, J.Johnson, M.C.Matthews, D.Mroczkowski, B.Parge, H.Vanarsdale, T.Popoff, I.Piraino, J.Margosiak, S.Thomson, J.Los, G.Murray, B.W.

(2009) Bioorg Med Chem Lett 19: 5613-5616

  • DOI: https://doi.org/10.1016/j.bmcl.2009.08.034
  • Primary Citation of Related Structures:  
    3IK8, 3IKD, 3IKG

  • PubMed Abstract: 

    Pin1 is a member of the cis-trans peptidyl-prolyl isomerase family with potential anti-cancer therapeutic value. Here we report structure-based de novo design and optimization of novel Pin1 inhibitors. Without a viable lead from internal screenings, we designed a series of novel Pin1 inhibitors by interrogating and exploring a protein crystal structure of Pin1. The ligand efficiency of the initial concept molecule was optimized with integrated SBDD and parallel chemistry approaches, resulting in a more attractive lead series.


  • Organizational Affiliation

    Pfizer Global Research and Development, 10770 Science Center Drive, San Diego, CA 92121, USA. alex.guo@pfizer.com


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
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Work: 0.209 
  • R-Value Observed: 0.209 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 116.835α = 90
b = 35.815β = 100.334
c = 51.396γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
X-PLORmodel building
X-PLORrefinement
HKL-2000data reduction
HKL-2000data scaling
X-PLORphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-09-22
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2021-10-13
    Changes: Database references
  • Version 1.3: 2024-02-21
    Changes: Data collection