3QCE

Human receptor protein tyrosine phosphatase gamma, domain 1, in complex with 3-[(3,4-dichlorobenzyl)sulfanyl]thiophene-2-carboxylic acid via soaking


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.261 
  • R-Value Work: 0.233 
  • R-Value Observed: 0.234 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

Small molecule receptor protein tyrosine phosphatase [gamma](RPTP[gamma]) ligands that inhibit phosphatase activity via perturbation of the tryptophan-proline-aspartate (WPD) loop

Sheriff, S.Beno, B.R.Zhai, W.Kostich, W.A.McDonnell, P.A.Kish, K.Goldfarb, V.Gao, M.Kiefer, S.E.Yanchunas, J.Huang, Y.Shi, S.Zhu, S.Dzierba, C.Bronson, J.Macor, J.E.Appiah, K.K.Westphal, R.S.O'Connell, J.Gerritz, S.W.

(2011) J Med Chem 54: 6548-6562

  • DOI: https://doi.org/10.1021/jm2003766
  • Primary Citation of Related Structures:  
    3QCB, 3QCC, 3QCD, 3QCE, 3QCF, 3QCG, 3QCH, 3QCI, 3QCJ, 3QCK, 3QCL, 3QCM, 3QCN

  • PubMed Abstract: 

    Protein tyrosine phosphatases (PTPs) catalyze the dephosphorylation of tyrosine residues, a process that involves a conserved tryptophan-proline-aspartate (WPD) loop in catalysis. In previously determined structures of PTPs, the WPD-loop has been observed in either an "open" conformation or a "closed" conformation. In the current work, X-ray structures of the catalytic domain of receptor-like protein tyrosine phosphatase γ (RPTPγ) revealed a ligand-induced "superopen" conformation not previously reported for PTPs. In the superopen conformation, the ligand acts as an apparent competitive inhibitor and binds in a small hydrophobic pocket adjacent to, but distinct from, the active site. In the open and closed WPD-loop conformations of RPTPγ, the side chain of Trp1026 partially occupies this pocket. In the superopen conformation, Trp1026 is displaced allowing a 3,4-dichlorobenzyl substituent to occupy this site. The bound ligand prevents closure of the WPD-loop over the active site and disrupts the catalytic cycle of the enzyme.


  • Organizational Affiliation

    Bristol-Myers Squibb Research and Development, P.O. Box 4000, Princeton, New Jersey 08543-4000, United States. steven.sheriff@bms.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Receptor-type tyrosine-protein phosphatase gamma
A, B
310Homo sapiensMutation(s): 0 
Gene Names: PTPGPTPRG
EC: 3.1.3.48
UniProt & NIH Common Fund Data Resources
Find proteins for P23470 (Homo sapiens)
Explore P23470 
Go to UniProtKB:  P23470
PHAROS:  P23470
GTEx:  ENSG00000144724 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP23470
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
NXY BindingDB:  3QCE Ki: 2500 (nM) from 1 assay(s)
IC50: min: 2500, max: 1.28e+4 (nM) from 3 assay(s)
PDBBind:  3QCE Ki: 2500 (nM) from 1 assay(s)
Binding MOAD:  3QCE Ki: 2500 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.261 
  • R-Value Work: 0.233 
  • R-Value Observed: 0.234 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 74.9α = 90
b = 82.5β = 90
c = 127γ = 90
Software Package:
Software NamePurpose
CNSrefinement
PDB_EXTRACTdata extraction
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing
CNXrefinement

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2011-12-28 
  • Deposition Author(s): Sheriff, S.

Revision History  (Full details and data files)

  • Version 1.0: 2011-12-28
    Type: Initial release
  • Version 1.1: 2023-09-13
    Changes: Data collection, Database references, Derived calculations, Refinement description