1PYN

DUAL-SITE POTENT, SELECTIVE PROTEIN TYROSINE PHOSPHATASE 1B INHIBITOR USING A LINKED FRAGMENT STRATEGY AND A MALONATE HEAD ON THE FIRST SITE


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.224 
  • R-Value Work: 0.198 
  • R-Value Observed: 0.211 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Discovery and SAR of novel, potent and selective protein tyrosine phosphatase 1B inhibitors.

Pei, Z.Li, X.Liu, G.Abad-Zapatero, C.Lubben, T.Zhang, T.Ballaron, S.J.Hutchins, C.W.Trevillyan, J.M.Jirousek, M.R.

(2003) Bioorg Med Chem Lett 13: 3129-3132

  • DOI: https://doi.org/10.1016/s0960-894x(03)00725-x
  • Primary Citation of Related Structures:  
    1PYN

  • PubMed Abstract: 

    A salicylate second site binder was linked to three classes of phosphotyrosine mimetics to produce potent protein tyrosine phosphatase 1B (PTP1B) inhibitors which exhibit significant selectivity against other phosphatases including the most homologous member, TCPTP.


  • Organizational Affiliation

    Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6098, USA. zhonghua.pei@abbott.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Protein-tyrosine phosphatase, non-receptor type 1321Homo sapiensMutation(s): 0 
Gene Names: PTPN1 OR PTP1B
EC: 3.1.3.48
UniProt & NIH Common Fund Data Resources
Find proteins for P18031 (Homo sapiens)
Explore P18031 
Go to UniProtKB:  P18031
PHAROS:  P18031
GTEx:  ENSG00000196396 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP18031
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
941
Query on 941

Download Ideal Coordinates CCD File 
B [auth A]2-(4-{2-TERT-BUTOXYCARBONYLAMINO-2-[4-(3-HYDROXY-2-METHOXYCARBONYL-PHENOXY)-BUTYLCARBAMOYL]-ETHYL}-PHENOXY)-MALONIC ACID
C29 H36 N2 O12
GFLFMVSYYFLPFQ-IBGZPJMESA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
941 BindingDB:  1PYN Ki: min: 3200, max: 3981 (nM) from 3 assay(s)
Binding MOAD:  1PYN Ki: 3200 (nM) from 1 assay(s)
PDBBind:  1PYN Ki: 3200 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.224 
  • R-Value Work: 0.198 
  • R-Value Observed: 0.211 
  • Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 88.71α = 90
b = 88.71β = 90
c = 104.83γ = 120
Software Package:
Software NamePurpose
MAR345data collection
HKL-2000data reduction
CNXrefinement
HKL-2000data scaling
CNXphasing

Structure Validation

View Full Validation Report



Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2003-09-16
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-10-11
    Changes: Refinement description
  • Version 1.4: 2023-08-16
    Changes: Data collection, Database references, Derived calculations, Refinement description