O-GlcNAcase: Promiscuous Hexosaminidase or Key Regulator of O-GlcNAc Signaling?

Alonso, Jana; Schimpl, M.; Aalten, Daan M. F. van

doi:10.1074/jbc.r114.609198

Cited by 58 publications

(53 citation statements)

References 83 publications

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“…Insight into potential mechanisms governing OGA substrate recognition has been limited by the lack of a crystal structure for a eukaryotic OGA 43 . However, multiple studies have elucidated the structures of bacterial glycosidases that are close homologs of human OGA, some of which have been shown to possess in vitro O -GlcNAc hydrolase activity toward human proteins 44, 45 .…”

Section: Substrate Recognition By Ogt and Ogamentioning

confidence: 99%

Protein O-GlcNAcylation: emerging mechanisms and functions

Yang

Qian

2017

Nat Rev Mol Cell Biol

895

869

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O-GlcNAcylation—the attachment of O-linked N-acetylglucosamine (O-GlcNAc) moieties to cytoplasmic, nuclear and mitochondrial proteins—is a post-translational modification that regulates fundamental cellular processes in metazoans. A single pair of enzymes—O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA)—controls the dynamic cycling of this post-translational modification in a nutrient- and stress-responsive manner. Recent years have seen remarkable advances in our understanding of O-GlcNAcylation at levels ranging from structural and molecular biology to cell signalling and gene regulation to physiology and disease. Emerging from these recent developments are new mechanisms and functions of O-GlcNAcylation that enable us to begin constructing a unified conceptual framework through which to understand the significance of this modification in cellular and organismal physiology.

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Section: Substrate Recognition By Ogt and Ogamentioning

confidence: 99%

Protein O-GlcNAcylation: emerging mechanisms and functions

Yang

Qian

2017

Nat Rev Mol Cell Biol

895

869

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“…The hexosaminidase O-GlcNAc hydrolase (OGA) is responsible for O-GlcNAc removal (92). OGT and OGA together allow for dynamic cycling of OGlcNAc on proteins (93,94).…”

Section: Protein Glycosylationmentioning

confidence: 99%

The Biochemistry of O-GlcNAc Transferase: Which Functions Make It Essential in Mammalian Cells?

Levine

Walker

2016

Annu. Rev. Biochem.

169

165

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O-linked N-acetylglucosamine transferase (OGT) is found in all metazoans and plays an important role in development but at the single-cell level is only essential in dividing mammalian cells. Postmitotic mammalian cells and cells of invertebrates such as Caenorhabditis elegans and Drosophila can survive without copies of OGT. Why OGT is required in dividing mammalian cells but not in other cells remains unknown. OGT has multiple biochemical activities. Beyond its well-known role in adding β-O-GlcNAc to serine and threonine residues of nuclear and cytoplasmic proteins, OGT also acts as a protease in the maturation of the cell cycle regulator host cell factor 1 (HCF-1) and serves as an integral member of several protein complexes, many of them linked to gene expression. In this review, we summarize current understanding of the mechanisms underlying OGT's biochemical activities and address whether known functions of OGT could be related to its essential role in dividing mammalian cells.

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“…21,22 OGA was recently found to be very sensitive to a substitution of the N-acyl group of O-GlcNAc. The extension of this group in a substrate can markedly decrease the hydrolyzing efficiency of OGA.…”

mentioning

confidence: 99%

Site-Directed Glycosylation of Peptide/Protein with Homogeneous O-Linked Eukaryotic N-Glycans

Jiang

Zhu

et al. 2016

Bioconjugate Chem.

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Here we report a facile and efficient method for site-directed glycosylation of peptide/protein. The method contains two sequential steps: generation of a GlcNAc-O-peptide/protein, and subsequent ligation of a eukaryotic N-glycan to the GlcNAc moiety. A pharmaceutical peptide, glucagon-like peptide-1 (GLP-1), and a model protein, bovine α-Crystallin, were successfully glycosylated using such an approach. It was shown that the GLP-1 with O-linked N-glycan maintained an unchanged secondary structure after glycosylation, suggesting the potential application of this approach for peptide/protein drug production. In summary, the coupled approach provides a general strategy to produce homogeneous glycopeptide/glycoprotein bearing eukaryotic N-glycans.

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O-GlcNAcase: Promiscuous Hexosaminidase or Key Regulator of O-GlcNAc Signaling?

Cited by 58 publications

References 83 publications

Protein O-GlcNAcylation: emerging mechanisms and functions

Protein O-GlcNAcylation: emerging mechanisms and functions

The Biochemistry of O-GlcNAc Transferase: Which Functions Make It Essential in Mammalian Cells?

Site-Directed Glycosylation of Peptide/Protein with Homogeneous O-Linked Eukaryotic N-Glycans

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