Enzyme spotlights
Documentation
EC 1.2.1.12
glyceraldehyde-3-phosphate dehydrogenase (phosphorylating)
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.
Reference:
High-resolution structure of human D-glyceraldehyde-3-phosphate dehydrogenase. Acta Crystallogr. D 62, 290-301. [PMID: 16510976]