5QER

PanDDA analysis group deposition -- Crystal structure of PTP1B in complex with compound_FMSOA000847b


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.73 Å
  • R-Value Free: 0.234 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.205 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

An expanded allosteric network in PTP1B by multitemperature crystallography, fragment screening, and covalent tethering.

Keedy, D.A.Hill, Z.B.Biel, J.T.Kang, E.Rettenmaier, T.J.Brandao-Neto, J.Pearce, N.M.von Delft, F.Wells, J.A.Fraser, J.S.

(2018) Elife 7

  • DOI: https://doi.org/10.7554/eLife.36307

  • PubMed Abstract: 

    Allostery is an inherent feature of proteins, but it remains challenging to reveal the mechanisms by which allosteric signals propagate. A clearer understanding of this intrinsic circuitry would afford new opportunities to modulate protein function. Here, we have identified allosteric sites in protein tyrosine phosphatase 1B (PTP1B) by combining multiple-temperature X-ray crystallography experiments and structure determination from hundreds of individual small-molecule fragment soaks. New modeling approaches reveal 'hidden' low-occupancy conformational states for protein and ligands. Our results converge on allosteric sites that are conformationally coupled to the active-site WPD loop and are hotspots for fragment binding. Targeting one of these sites with covalently tethered molecules or mutations allosterically inhibits enzyme activity. Overall, this work demonstrates how the ensemble nature of macromolecular structure, revealed here by multitemperature crystallography, can elucidate allosteric mechanisms and open new doors for long-range control of protein function.


  • Organizational Affiliation

    Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, United States.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Tyrosine-protein phosphatase non-receptor type 1321Homo sapiensMutation(s): 2 
Gene Names: PTPN1PTP1B
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
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.73 Å
  • R-Value Free: 0.234 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.205 
  • Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 89.723α = 90
b = 89.723β = 90
c = 106.32γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
XSCALEdata scaling
PHASERphasing
PDB_EXTRACTdata extraction
XDSdata reduction

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2018-10-10
    Type: Initial release
  • Version 1.1: 2019-02-06
    Changes: Data collection, Database references, Structure summary
  • Version 1.2: 2024-10-23
    Changes: Data collection, Database references, Structure summary