4MA4

S-glutathionylated PFKFB3


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.23 Å
  • R-Value Free: 0.242 
  • R-Value Work: 0.199 
  • R-Value Observed: 0.202 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

PFKFB3 Regulates Oxidative Stress Homeostasis via Its S-Glutathionylation in Cancer.

Seo, M.Lee, Y.H.

(2014) J Mol Biol 426: 830-842

  • DOI: https://doi.org/10.1016/j.jmb.2013.11.021
  • Primary Citation of Related Structures:  
    4MA4

  • PubMed Abstract: 

    Whereas moderately increased cellular oxidative stress is supportive for cancerous growth of cells, excessive levels of reactive oxygen species (ROS) are detrimental to their growth and survival. We demonstrated that high ROS levels, via increased oxidized glutathione (GSSG), induce isoform-specific S-glutathionylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) at residue Cys206, which is located near the entrance to the 6-phosphofructo-2-kinase catalytic pocket. Upon this ROS-dependent, reversible, covalent modification, a marked decrease in its catalytic ability to synthesize fructose-2,6-bisphosphate (Fru-2,6-P₂), the key glycolysis allosteric activator, was observed. This event was coupled to a decrease in glycolytic flux and an increase in glucose metabolic flux into the pentose phosphate pathway. This shift, in turn, caused an increase in reduced glutathione (GSH) and, ultimately, resulted in ROS detoxification inside HeLa cells. The ability of PFKFB3 to control the Fru-2,6-P₂ levels in an ROS-dependent manner allows the PFKFB3-expressing cancer cells to continue energy metabolism with a reduced risk of excessive oxidative stress and, thereby, to support their cell survival and proliferation. This study provides a new insight into the roles of PFKFB3 as switch that senses and controls redox homeostasis in cancer in addition to its role in cancer glycolysis.


  • Organizational Affiliation

    Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3520Homo sapiensMutation(s): 0 
Gene Names: PFKFB3
EC: 2.7.1.105 (PDB Primary Data), 3.1.3.46 (PDB Primary Data)
UniProt & NIH Common Fund Data Resources
Find proteins for Q16875 (Homo sapiens)
Explore Q16875 
Go to UniProtKB:  Q16875
PHAROS:  Q16875
GTEx:  ENSG00000170525 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ16875
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ADP
Query on ADP

Download Ideal Coordinates CCD File 
B [auth A]ADENOSINE-5'-DIPHOSPHATE
C10 H15 N5 O10 P2
XTWYTFMLZFPYCI-KQYNXXCUSA-N
GSH
Query on GSH

Download Ideal Coordinates CCD File 
E [auth A]GLUTATHIONE
C10 H17 N3 O6 S
RWSXRVCMGQZWBV-WDSKDSINSA-N
F6P
Query on F6P

Download Ideal Coordinates CCD File 
G [auth A]6-O-phosphono-beta-D-fructofuranose
C6 H13 O9 P
BGWGXPAPYGQALX-ARQDHWQXSA-N
MLA
Query on MLA

Download Ideal Coordinates CCD File 
C [auth A],
F [auth A]
MALONIC ACID
C3 H4 O4
OFOBLEOULBTSOW-UHFFFAOYSA-N
ACY
Query on ACY

Download Ideal Coordinates CCD File 
D [auth A]ACETIC ACID
C2 H4 O2
QTBSBXVTEAMEQO-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.23 Å
  • R-Value Free: 0.242 
  • R-Value Work: 0.199 
  • R-Value Observed: 0.202 
  • Space Group: P 65 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 102.508α = 90
b = 102.508β = 90
c = 260.606γ = 120
Software Package:
Software NamePurpose
XDSdata scaling
PHASESphasing
REFMACrefinement
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: 2013-12-11
    Type: Initial release
  • Version 1.1: 2013-12-25
    Changes: Database references
  • Version 1.2: 2014-02-12
    Changes: Database references
  • Version 1.3: 2015-04-29
    Changes: Non-polymer description
  • Version 1.4: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Derived calculations, Structure summary