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spinqualitylabelsall models Human OGA complex with PUGNAC type inhibitor (PDB code 5m7t Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Function O-GlcNAcase or hyaluronoglucosaminidase (OGA) is one of two enzymes which modulate the level of O-linked N-acetylglucosamine (O-GlcNAc) attachment to cytoplasmic, nuclear and mitochondrial proteins[1]. The attachment of O-GlcNAc to proteins is a post-translational modification. Relevance Inhibition of OGA is a promising therapeutic approach to treat tau pathology in neurodegenerative diseases such as Alzheimer's disease and progressive supranuclear palsy[2]. The inhibition of OGA hinders formation of tau aggregates and decreases neuronal cell loss[3]. Structural highlights The 3D structure of the complex between human OGA and a PUGNAC type inhibitor shows the active site pocket at the base of a V-shaped cleft between the 2 OGA monomers.

3D structures of O-GlcNAcase

Updated on 02-October-2020

References

1. ↑ Shen DL, Gloster TM, Yuzwa SA, Vocadlo DJ. Insights into O-linked N-acetylglucosamine ([0-9]O-GlcNAc) processing and dynamics through kinetic analysis of O-GlcNAc transferase and O-GlcNAcase activity on protein substrates. J Biol Chem. 2012 May 4;287(19):15395-408. doi: 10.1074/jbc.M111.310664. Epub, 2012 Feb 6. PMID:22311971 doi:http://dx.doi.org/10.1074/jbc.M111.310664
2. ↑ Selnick HG, Hess JF, Tang C, Liu K, Schachter JB, Ballard JE, Marcus J, Klein DJ, Wang X, Pearson M, Savage MJ, Kaul R, Li TS, Vocadlo DJ, Zhou Y, Zhu Y, Mu C, Wang Y, Wei Z, Bai C, Duffy JL, McEachern EJ. Discovery of MK-8719, a Potent O-GlcNAcase Inhibitor as a Potential Treatment for Tauopathies. J Med Chem. 2019 Nov 27;62(22):10062-10097. doi: 10.1021/acs.jmedchem.9b01090., Epub 2019 Sep 29. PMID:31487175 doi:http://dx.doi.org/10.1021/acs.jmedchem.9b01090
3. ↑ Yuzwa SA, Shan X, Macauley MS, Clark T, Skorobogatko Y, Vosseller K, Vocadlo DJ. Increasing O-GlcNAc slows neurodegeneration and stabilizes tau against aggregation. Nat Chem Biol. 2012 Feb 26;8(4):393-9. doi: 10.1038/nchembio.797. PMID:22366723 doi:http://dx.doi.org/10.1038/nchembio.797