4GWG

Crystal Structure Analysis of 6-phosphogluconate dehydrogenase apo-form


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.39 Å
  • R-Value Free: 0.186 
  • R-Value Work: 0.169 
  • R-Value Observed: 0.170 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Phosphoglycerate mutase 1 coordinates glycolysis and biosynthesis to promote tumor growth.

Hitosugi, T.Zhou, L.Elf, S.Fan, J.Kang, H.B.Seo, J.H.Shan, C.Dai, Q.Zhang, L.Xie, J.Gu, T.L.Jin, P.Aleckovic, M.Leroy, G.Kang, Y.Sudderth, J.A.Deberardinis, R.J.Luan, C.H.Chen, G.Z.Muller, S.Shin, D.M.Owonikoko, T.K.Lonial, S.Arellano, M.L.Khoury, H.J.Khuri, F.R.Lee, B.H.Ye, K.Boggon, T.J.Kang, S.He, C.Chen, J.

(2012) Cancer Cell 22: 585-600

  • DOI: https://doi.org/10.1016/j.ccr.2012.09.020
  • Primary Citation of Related Structures:  
    4GWG, 4GWK

  • PubMed Abstract: 

    It is unclear how cancer cells coordinate glycolysis and biosynthesis to support rapidly growing tumors. We found that the glycolytic enzyme phosphoglycerate mutase 1 (PGAM1), commonly upregulated in human cancers due to loss of TP53, contributes to biosynthesis regulation in part by controlling intracellular levels of its substrate, 3-phosphoglycerate (3-PG), and product, 2-phosphoglycerate (2-PG). 3-PG binds to and inhibits 6-phosphogluconate dehydrogenase in the oxidative pentose phosphate pathway (PPP), while 2-PG activates 3-phosphoglycerate dehydrogenase to provide feedback control of 3-PG levels. Inhibition of PGAM1 by shRNA or a small molecule inhibitor PGMI-004A results in increased 3-PG and decreased 2-PG levels in cancer cells, leading to significantly decreased glycolysis, PPP flux and biosynthesis, as well as attenuated cell proliferation and tumor growth.


  • Organizational Affiliation

    Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
6-phosphogluconate dehydrogenase, decarboxylating484Homo sapiensMutation(s): 0 
Gene Names: PGDPGDH
EC: 1.1.1.44
UniProt & NIH Common Fund Data Resources
Find proteins for P52209 (Homo sapiens)
Explore P52209 
Go to UniProtKB:  P52209
PHAROS:  P52209
GTEx:  ENSG00000142657 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP52209
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
MES
Query on MES

Download Ideal Coordinates CCD File 
B [auth A],
C [auth A]
2-(N-MORPHOLINO)-ETHANESULFONIC ACID
C6 H13 N O4 S
SXGZJKUKBWWHRA-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.39 Å
  • R-Value Free: 0.186 
  • R-Value Work: 0.169 
  • R-Value Observed: 0.170 
  • Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 87.28α = 90
b = 87.28β = 90
c = 130.892γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
PHASESphasing
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-11-28
    Type: Initial release
  • Version 1.1: 2012-12-05
    Changes: Data collection
  • Version 1.2: 2018-01-24
    Changes: Structure summary
  • Version 1.3: 2023-09-13
    Changes: Data collection, Database references, Derived calculations, Refinement description