Enzymes for Research, Diagnostic and Industrial Use
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| Catalog | Product Name | EC No. | CAS No. | Source | Price |
|---|---|---|---|---|---|
| NATE-0496 | O-Glycanase from Streptococcus pneumoniae, Recombinant | E. coli | Inquiry |
O-glucanase, also known as O-GlcNAcase or OGA, is an enzyme that selectively cleaves O-linked N-acetylglucosamine (O-GlcNAc) from proteins in eukaryotic cells. This enzyme plays an important role in the regulation of many cellular processes, including transcriptional regulation, signal transduction, and cell cycle progression. This article will explore the background, structure, mechanism of action, clinical significance and potential applications of O-glycosaminidase.
O-GlcNAc modification is a reversible post-translational modification (PTM) that involves the attachment of a single N-acetylglucosaminoglycan to the hydroxyl groups of serine and threonine residues of the target protein. This modification has a key role in the regulation of various cellular functions, including gene expression, cellular metabolism and protein signaling. The addition and removal of O-GlcNAc molecules on proteins is catalyzed by two enzymes: O-linked N-acetyl glucosamine transferase (OGT) and O-Glycanase.
O-Glycanase is a member of the glycoside hydrolase family 84 and is highly conserved across species, from bacteria to humans. This enzyme is composed of a single polypeptide chain and possesses a complex hierarchical structure that comprises multiple domains and sites. The catalytic domain of the enzyme consists of a (β/α)8 barrel that forms the central core of the protein. The catalytic residues (D174, D175, and E326) are located within the barrel.
O-Glycanase catalyzes the hydrolysis of β-linked N-acetylglucosamine residues from targeted proteins through a catalytic mechanism that involves the protonation of the β-glycosidic oxygen atom of the N-acetylglucosamine moiety by an aspartic acid residue (D174). This reaction generates a covalent intermediate between D174 and the carbohydrate substrate. Subsequently, the intermediate is resolved by nucleophilic attack on the anomeric carbon atom of the sugar by a water molecule, concomitantly transferring the GlcNAc residue to the water molecule and the enzyme regains unmodified serine/threonine residue on the protein. The crystal structures of O-Glycanase in complex with its substrates suggest that the enzyme selectively cleaves GlcNAc residues attached to serine/threonine residues of target proteins.
O-Glycanase has been implicated in various cellular processes, including cytoskeletal dynamics, cell cycle progression, and transcriptional regulation. Studies have shown that O-Glycanase regulates the activity, localization, and stability of proteins, as well as signaling pathways. Dysregulation of O-Glycanase activity or the O-GlcNAc modification is associated with a range of human diseases, including cancer, neurodegeneration, and diabetes.
Dysregulated O-GlcNAcylation, mainly due to upregulated OGT activity and O-Glycanase down-regulation, has been observed in a variety of tumors. The maintenance of a high O-GlcNAcylation profile of proteins, such as tau protein and c-Myc, has been shown to contribute to cancer cell growth and progression. O-Glycanase overexpression studies have been shown to reduce cancer cell proliferation, migration and invasion, indicating that O-Glycanase is a potential tumor suppressor in some cancers.
The therapeutic potential of O-Glycanase lies in its ability to regulate the O-GlcNAcylation of proteins selectively. The development of O-Glycanase inhibitors and activators may provide new therapeutic approaches for treating human diseases in which dysregulated O-Glycanase activity contributes to pathogenesis. The use of O-Glycanase and O-GlcNAc inhibitors as potential therapeutic agents have not only been explored in cancer but also in other diseases, like AD and diabetes.
Overall, O-Glycanase is a critical enzyme involved in regulating the O-GlcNAc cycling of eukaryotic cells, which is involved in numerous cellular processes and has been implicated in human disease. The structure, mechanism of action, and clinical significance reveal a promising target for the treatment of various diseases. The pharmaceutical industry is now considering the development of selective O-Glycanase inhibitors and activators as potential therapeutic agents for various human diseases with dysregulated O-Glycanase activity and glycosylation patterns.
