| Structural highlights
Function
OGA_HUMAN Isoform 1: Cleaves GlcNAc but not GalNAc from O-glycosylated proteins. Can use p-nitrophenyl-beta-GlcNAc and 4-methylumbelliferone-GlcNAc as substrates but not p-nitrophenyl-beta-GalNAc or p-nitrophenyl-alpha-GlcNAc (in vitro) (PubMed:11148210). Does not bind acetyl-CoA and does not have histone acetyltransferase activity (PubMed:24088714).[1] [2] [3] [4] [5] Isoform 3: Cleaves GlcNAc but not GalNAc from O-glycosylated proteins. Can use p-nitrophenyl-beta-GlcNAc as substrate but not p-nitrophenyl-beta-GalNAc or p-nitrophenyl-alpha-GlcNAc (in vitro), but has about six times lower specific activity than isoform 1.[6]
Publication Abstract from PubMed
O-GlcNAc hydrolase (OGA) removes O-linked N-acetylglucosamine (O-GlcNAc) from a myriad of nucleocytoplasmic proteins. Through co-expression and assembly of OGA fragments, we determined the three-dimensional structure of human OGA, revealing an unusual helix-exchanged dimer that lays a structural foundation for an improved understanding of substrate recognition and regulation of OGA. Structures of OGA in complex with a series of inhibitors define a precise blueprint for the design of inhibitors that have clinical value.
Structural and functional insight into human O-GlcNAcase.,Roth C, Chan S, Offen WA, Hemsworth GR, Willems LI, King DT, Varghese V, Britton R, Vocadlo DJ, Davies GJ Nat Chem Biol. 2017 Mar 27. doi: 10.1038/nchembio.2358. PMID:28346405[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gao Y, Wells L, Comer FI, Parker GJ, Hart GW. Dynamic O-glycosylation of nuclear and cytosolic proteins: cloning and characterization of a neutral, cytosolic beta-N-acetylglucosaminidase from human brain. J Biol Chem. 2001 Mar 30;276(13):9838-45. Epub 2001 Jan 8. PMID:11148210 doi:https://dx.doi.org/10.1074/jbc.M010420200
- ↑ Wells L, Gao Y, Mahoney JA, Vosseller K, Chen C, Rosen A, Hart GW. Dynamic O-glycosylation of nuclear and cytosolic proteins: further characterization of the nucleocytoplasmic beta-N-acetylglucosaminidase, O-GlcNAcase. J Biol Chem. 2002 Jan 18;277(3):1755-61. PMID:11788610
- ↑ Li J, Huang CL, Zhang LW, Lin L, Li ZH, Zhang FW, Wang P. Isoforms of human O-GlcNAcase show distinct catalytic efficiencies. Biochemistry (Mosc). 2010 Jul;75(7):938-43. PMID:20673219
- ↑ Schimpl M, Borodkin VS, Gray LJ, van Aalten DM. Synergy of Peptide and Sugar in O-GlcNAcase Substrate Recognition. Chem Biol. 2012 Feb 24;19(2):173-8. PMID:22365600 doi:10.1016/j.chembiol.2012.01.011
- ↑ Rao FV, Schuttelkopf AW, Dorfmueller HC, Ferenbach AT, Navratilova I, van Aalten DM. Structure of a bacterial putative acetyltransferase defines the fold of the human O-GlcNAcase C-terminal domain. Open Biol. 2013 Oct 2;3(10):130021. PMID:24088714 doi:https://dx.doi.org/10.1098/rsob.130021
- ↑ Li J, Huang CL, Zhang LW, Lin L, Li ZH, Zhang FW, Wang P. Isoforms of human O-GlcNAcase show distinct catalytic efficiencies. Biochemistry (Mosc). 2010 Jul;75(7):938-43. PMID:20673219
- ↑ Roth C, Chan S, Offen WA, Hemsworth GR, Willems LI, King DT, Varghese V, Britton R, Vocadlo DJ, Davies GJ. Structural and functional insight into human O-GlcNAcase. Nat Chem Biol. 2017 Mar 27. doi: 10.1038/nchembio.2358. PMID:28346405 doi:https://dx.doi.org/10.1038/nchembio.2358
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