5H08

Human PTPRZ D1 domain complexed with NAZ2329


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.53 Å
  • R-Value Free: 0.297 
  • R-Value Work: 0.210 
  • R-Value Observed: 0.215 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Targeting PTPRZ inhibits stem cell-like properties and tumorigenicity in glioblastoma cells

Fujikawa, A.Sugawara, H.Tanaka, T.Matsumoto, M.Kuboyama, K.Suzuki, R.Tanga, N.Ogata, A.Masumura, M.Noda, M.

(2017) Sci Rep 7: 5609-5609

  • DOI: https://doi.org/10.1038/s41598-017-05931-8
  • Primary Citation of Related Structures:  
    5H08

  • PubMed Abstract: 

    The R5 subfamily of receptor-type protein tyrosine phosphatases (RPTPs) comprises PTPRZ and PTPRG. A recent study on primary human glioblastomas suggested a close association between PTPRZ1 (human PTPRZ) expression and cancer stemness. However, the functional roles of PTPRZ activity in glioma stem cells have remained unclear. In the present study, we found that sphere-forming cells from the rat C6 and human U251 glioblastoma cell lines showed high expression levels of PTPRZ-B, the short receptor isoform of PTPRZ. Stable PTPRZ knockdown altered the expression levels of stem cell transcription factors such as SOX2, OLIG2, and POU3F2 and decreased the sphere-forming abilities of these cells. Suppressive effects on the cancer stem-like properties of the cells were also observed following the knockdown of PTPRG. Here, we identified NAZ2329, a cell-permeable small molecule that allosterically inhibits both PTPRZ and PTPRG. NAZ2329 reduced the expression of SOX2 in C6 and U251 cells and abrogated the sphere-forming abilities of these cells. Tumor growth in the C6 xenograft mouse model was significantly slower with the co-treatment of NAZ2329 with temozolomide, an alkylating agent, than with the individual treatments. These results indicate that pharmacological inhibition of R5 RPTPs is a promising strategy for the treatment of malignant gliomas.


  • Organizational Affiliation

    Division of Molecular Neurobiology, National Institute for Basic Biology (NIBB), 5-1 Higashiyama, Myodaiji-cho, Okazaki, Aichi, 444-8787, Japan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Receptor-type tyrosine-protein phosphatase zeta298Homo sapiensMutation(s): 0 
Gene Names: PTPRZ1HTPZP2PTPRZPTPRZ2PTPZ
EC: 3.1.3.48
UniProt & NIH Common Fund Data Resources
Find proteins for P23471 (Homo sapiens)
Explore P23471 
Go to UniProtKB:  P23471
PHAROS:  P23471
GTEx:  ENSG00000106278 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP23471
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
7WL
Query on 7WL

Download Ideal Coordinates CCD File 
B [auth A]3-{[2-Ethoxy-5-(trifluoromethyl)benzyl]sulfanyl}-N-(phenylsulfonyl)thiophene-2-carboxamide
C21 H18 F3 N O4 S3
AKXBLDKCMACKRY-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.53 Å
  • R-Value Free: 0.297 
  • R-Value Work: 0.210 
  • R-Value Observed: 0.215 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 53.776α = 90
b = 72.306β = 90
c = 90.796γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling
AMoREphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data

  • Released Date: 2017-07-26 
  • Deposition Author(s): Sugawara, H.

Funding OrganizationLocationGrant Number
Japan Agency for Medical Research and developmentJapan15im0110409b0104

Revision History  (Full details and data files)

  • Version 1.0: 2017-07-26
    Type: Initial release
  • Version 1.1: 2017-08-16
    Changes: Database references
  • Version 1.2: 2023-11-08
    Changes: Data collection, Database references, Refinement description