4MA4

S-glutathionylated PFKFB3

4MA4 の概要

• エントリーDOI: 10.2210/pdb4ma4/pdb
• 関連するPDBエントリー: 2axn 3QPW
• 分子名称: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3, ADENOSINE-5'-DIPHOSPHATE, MALONIC ACID, ... (7 entities in total)
• 機能のキーワード: s-glutathionylated protein, rossmann fold, phosphoryl transferase, s-glutathionylation, cytosol, hydrolase, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 60956.97

構造登録者

Lee, Y.-H.,Seo, M.-S. (登録日: 2013-08-15, 公開日: 2013-12-11, 最終更新日: 2025-03-26)

主引用文献

Seo, M.,Lee, Y.H.
PFKFB3 Regulates Oxidative Stress Homeostasis via Its S-Glutathionylation in Cancer.
J.Mol.Biol., 426:830-842, 2014

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.

PubMed: 24295899
DOI: 10.1016/j.jmb.2013.11.021

実験手法

X-RAY DIFFRACTION (2.23 Å)