Scientists reveal the crystal structure of Glycogen debranching enzyme (GDE)
Glycogen is a branched polymer of glucose and severs as a major energy store, its debranching by glycogen debranching enzyme (GDE) is crucial for its degradation and mobilization. Deficiency of GDE activity leads to the glycogen storage disease type III (GSDIII), and the clinical symptoms include hypoglycemia, growth retardation, hepatomegaly, hypertrophic cardiomyopathy and progressive skeletal myopathy.
A team of scientists led by Dr. Xiang Song from the Institute for Nutritional Sciences, SIBS, Chinese Academy of Sciences determined crystal structures of GDE and its complex with oligosaccharides, revealing its domain architecture and interactions with glycogen. Structure-guided mutagenesis combined with functional studies revealed that its two distinct domains catalyze sequential reactions in glycogen debranching, their catalytic mechanism and highly specific substrate recognition that are important for tightly regulated glycogen mobilization, and additional contacts with glycogen that facilitates the substrate recruitment of GDE and enhances its activity. This work revealed important mechanisms in controlled energy release from one of the body’s major fuel tanks, and elucidated the molecular mechanism for the disease-causing mutations in GDE.
This work was published online in Nature Communications on Apr 18, 2016, as a research article entitled "Crystal structure of glycogen debranching enzyme and insights into its catalysis and disease-causing mutations”. This study was funded by Chinese Academy of Sciences, the National Natural Science Foundation of China and Ministry of Science and Technology of China.
Xiang Song, Ph.D., Principal Investigator
Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Image by Dr. Xiang’ lab
Link to the article: http://www.nature.com/ncomms/2016/160418/ncomms11229/full/ncomms11229.html