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Evidence for a functional O-GlcNAc system in the thermophilic bacterium Thermobaculum terrenum

DOI: 10.1074/jbc.M115.689596 DOI Help
PMID: 26491011 PMID Help

Authors: Adam Ostrowski (University of Dundee) , Mehmet Gundogdu (University of Dundee) , Andrew T. Ferenbach (University of Dundee) , Andrey A. Lebedev (Science Technology Facilities Council) , Daan M. F. Van Aalten (University of Dundee)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Biological Chemistry

State: Published (Approved)
Published: October 2015

Open Access Open Access

Abstract: Post-translational modification of proteins is a ubiquitous mechanism of signal transduction in all kingdoms of life. One such modification is addition of O-linked N-acetylglucosamine to serine or threonine residues, known as O-GlcNAcylation. This unusual type of glycosylation is thought to be restricted to nucleocytoplasmic proteins of eukaryotes and is mediated by a pair of O-GlcNAc transferase and O-GlcNAc hydrolase enzymes operating on a large number of substrate proteins. Protein O-GlcNAcylation is responsive to glucose and flux through the hexosamine biosynthetic pathway. Thus, a close relationship is thought to exist between the level of O-GlcNAc proteins within and the general metabolic state of the cell. While isolated apparent orthologues of these enzymes are present in bacterial genomes, their biological functions remain largely unexplored. It is possible that understanding the function of these proteins will allow development of reductionist models to uncover the principles of O-GlcNAc signalling. Here, we identify orthologues of both O-GlcNAc cycling enzymes in the genome of the thermophilic eubacterium Thermobaculum terrenum. The O-GlcNAcase and O-GlcNAc transferase are co-expressed and, like their mammalian orthologues, localise to the cytoplasm. The O-GlcNAcase orthologue possesses activity against O-GlcNAc proteins and model substrates. We describe crystal structures of both enzymes, including an O-GlcNAcase-peptide complex, showing conservation of active sites with the human orthologues. Although in vitro activity of the O-GlcNAc transferase could not be detected, treatment of T. terrenum with an O-GlcNAc transferase inhibitor led to inhibition of growth. T. terrenum may be the first example of a bacterium possessing a functional O-GlcNAc system.

Journal Keywords: Electron Microscopy; Enzyme Kinetics; Glycosyltransferase; Gram-Positive Bacteria

Subject Areas: Biology and Bio-materials

Instruments: I04-Macromolecular Crystallography

Other Facilities: European Synchrotron Radiation Facility

Added On: 18/11/2015 14:09

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