Structural highlights
Function
[OGA_CLOP1] Biological function unknown. Capable of hydrolyzing the glycosidic link of O-GlcNAcylated proteins.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Streptozotocin is a natural product that selectively kills insulin-secreting beta cells, and is widely used to generate mouse models of diabetes or treat pancreatic tumors. Several studies suggest that streptozotocin toxicity stems from its N-nitrosourea moiety releasing nitric oxide and possessing DNA alkylating activity. However, it has also been proposed that streptozotocin induces apoptosis by inhibiting O-GlcNAcase, an enzyme that, together with O-GlcNAc transferase, is important for dynamic intracellular protein O-glycosylation. We have used galacto-streptozotocin to chemically dissect the link between O-GlcNAcase inhibition and apoptosis. Using X-ray crystallography, enzymology, and cell biological studies on an insulinoma cell line, we show that, whereas streptozotocin competitively inhibits O-GlcNAcase and induces apoptosis, its galacto-configured derivative no longer inhibits O-GlcNAcase, yet still induces apoptosis. This supports a general chemical poison mode of action for streptozotocin, suggesting the need for using more specific inhibitors to study protein O-GlcNAcylation.
Chemical dissection of the link between streptozotocin, O-GlcNAc, and pancreatic cell death.,Pathak S, Dorfmueller HC, Borodkin VS, van Aalten DM Chem Biol. 2008 Aug 25;15(8):799-807. PMID:18721751[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Pathak S, Dorfmueller HC, Borodkin VS, van Aalten DM. Chemical dissection of the link between streptozotocin, O-GlcNAc, and pancreatic cell death. Chem Biol. 2008 Aug 25;15(8):799-807. PMID:18721751 doi:10.1016/j.chembiol.2008.06.010