Chemical genetics and its application to moonlighting in glycolytic enzymes.
Glycolysis is an ancient biochemical pathway that breaks down glucose into pyruvate to produce ATP. The structural and catalytic properties of glycolytic enzymes are well-characterized. However, there is growing appreciation that these enzymes participate in numerous moonlighting functions that are unrelated to glycolysis. Recently, chemical genetics has been used to discover novel moonlighting functions in glycolytic enzymes. In the present mini-review, we introduce chemical genetics and discuss how it can be applied to the discovery of protein moonlighting. Specifically, we describe the application of chemical genetics to uncover moonlighting in two glycolytic enzymes, enolase and glyceraldehyde dehydrogenase. This led to the discovery of moonlighting roles in glucose homoeostasis, cancer progression and diabetes-related complications. Finally, we also provide a brief overview of the latest progress in unravelling the myriad moonlighting roles for these enzymes.
*New Drug Targets Laboratory, School of Life Sciences, Gwangju Institute of Science and Technology, 1 Oryong-Dong, Buk-Gu, Gwangju 500-712, Republic of Korea.
Da-Woon
DW
Jung
*New Drug Targets Laboratory, School of Life Sciences, Gwangju Institute of Science and Technology, 1 Oryong-Dong, Buk-Gu, Gwangju 500-712, Republic of Korea.
Woong-Hee
WH
Kim
*New Drug Targets Laboratory, School of Life Sciences, Gwangju Institute of Science and Technology, 1 Oryong-Dong, Buk-Gu, Gwangju 500-712, Republic of Korea.
Darren R
DR
Williams
D000818:Animals; D002384:Catalysis; D003920:Diabetes Mellitus / Q000201:enzymology / Q000503:physiopathology; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D007328:Insulin / Q000378:metabolism; D009369:Neoplasms / Q000201:enzymology / Q000503:physiopathology; D010751:Phosphopyruvate Hydratase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D007328:Insulin; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D010751:Phosphopyruvate Hydratase