Enzyme spotlights


glyceraldehyde-3-phosphate dehydrogenase (phosphorylating)

human GAPDH Abstract:
GAPDH is an NAD+-dependent glycolytic enzyme that catalyses the formation of 1,3-bisphosphoglycerate from glyceraldehyde-3-phosphate and phosphate . Once thought to solely play a role in glycolysis, mammalian GAPDH has been implicated in many other cellular activities, including apoptosis, nuclear RNA transport, DNA replication, DNA repair, RNase activity, microtubule bundling and membrane fusion. Accordingly, GAPDH is thought to play roles in many diseases, including Parkinson's disease, Alzheimer's disease, Huntington's disease, dentatorubropallidoluysian atrophy and prostate cancer. Knowledge of the three-dimensional structure of human GAPDH at high resolution would facilitate the development of specific inhibitors of GAPDHs from parasites as well as new anti-apoptosis drugs for the treatment of neurodegenerative diseases. The recently reported high-resolution (1.75 Å) crystal structure of human GAPDH provides an updated view of the NAD +-binding site, which is the target of inhibitors designed to combat parasitic diseases. The structure also provides a foundation for investigating the interactions between an anti-apoptosis compound CGP-3466 and human GAPDH.


Jenkins, J.L. and Tanner, J.J. (2006) High-resolution structure of human D-glyceraldehyde-3-phosphate dehydrogenase. Acta Crystallogr. D 62, 290-301. [PMID: 16510976]