About TIGAR:
TIGAR is a newly discovered enzyme that largely regulates glucose breakdown in human cells. In addition to its role in controlling glucose degradation, TIGAR activity can allow a cell to repair DNA and degrade its own organelles. Finally, TIGAR has the ability to shield a cell from death. Since its discovery in 2005 by Kuang-Yu Jen and Vivian G. Cheung, TIGAR has piqued the scientific community's interest due to its active role in various malignancies. The p53 tumor suppressor protein normally activates TIGAR production in the body when a cell has suffered low DNA damage or stress. TIGAR is under the control of other proteins in some malignancies. The goal is that future studies into TIGAR will lead to new cancer treatments.
TIGAR Structure
TIGAR has a tertiary structure similar to the histidine phosphatase fold and is approximately 30kDa. The core of TIGAR is a — sandwich composed of a six-stranded sheet encircled by four helices. To complete the enzyme, more helices and a lengthy loop are added around the core. TIGAR has a structurally similar active site to PhoE (a bacterial phosphatase enzyme) and a functionally similar active site to fructose-2,6-bisphosphatase.
TIGAR Function
TIGAR activation can have a variety of biological impacts. TIGAR works as a direct regulator of fructose-2,6-bisphosphate levels and hexokinase 2 activity, resulting in a cascade of metabolic reactions within the cell. TIGAR is a fructose bisphosphatase that activates p53, limiting glucose transporter expression and controlling the expression of hexokinase and phosphoglycerate mutase. TIGAR also inhibits Phosphofructokinase (PFK) by lowering the amount of fructose-2,6, bisphosphate, which inhibits glycolysis and promotes the pentose phosphate pathway.