By a News Reporter-Staff News Editor at Health & Medicine Week -- Current study results on Enzymes and Coenzymes have been published. According to news reporting originating in Kingston, Canada, by NewsRx journalists, research stated, "Modifications of proteins by O-glycosylation determine many of the properties and functions of proteins. We wish to understand the mechanisms of O-glycosylation and develop inhibitors that could affect glycoprotein functions and alter cellular behavior."
The news reporters obtained a quote from the research from Queen's University, "We expressed recombinant soluble human Gal- and GlcNAc-transferases that synthesize the O-glycan cores 1 to 4 and are critical for the overall structures of O-glycans. We determined the properties and substrate specificities of these enzymes using synthetic acceptor substrate analogs. Compounds that were inactive as substrates were tested as inhibitors. Enzymes significantly differed in their recognition of the sugar moieties and aglycone groups of substrates. Core I synthase was active with glycopeptide substrates but GlcNAc-transferases preferred substrates with hydrophobic aglycone groups. Chemical modifications of the acceptors shed light on enzyme-substrate interactions. Core 1 synthase was weakly inhibited by its substrate analog benzyl 2-butanamido-2-deoxy-alpha-D-galactoside while two of the three GlcNAc-transferases were selectively and potently inhibited by bis-imidazolium salts which are not substrate analogs. This work delineates the distinct specificities and properties of the enzymes that synthesize the common O-glycan core structures 1 to 4. New inhibitors were found that could selectively inhibit the synthesis of cores 1, 2 and 3 but not core 4. General significance: These studies help our understanding of the mechanisms of action of enzymes critical for O-glycosylation."
According to the news reporters, the research concluded: "The results may be useful for the re-engineering of O-glycosylation to determine the roles of O-glycans and the enzymes critical for O-glycosylation, and for biotechnology with potential therapeutic applications."
For more information on this research see: Acceptor specificities and selective inhibition of recombinant human Gal- and GlcNAc-transferases that synthesize core Structures 1, 2, 3 and 4 of O-glycans. Biochimica Et Biophysica Acta-General Subjects, 2013;1830(8):4274-4281. Biochimica Et Biophysica Acta-General Subjects can be contacted at: Elsevier Science Bv, PO Box 211, 1000 Ae Amsterdam, Netherlands (see also Enzymes and Coenzymes).
Our news correspondents report that additional information may be obtained by contacting Y. Gao, Queen's University, Dept. of Chem, Kingston, ON K7L 3N6, Canada. Additional authors for this research include R.P. Aryal, T.Z. Ju, R.D. Cummings, G. Gahlay, D.L. Jarvis, K.L. Matta, J.Z. Vlahakis, W.A. Szarek and I. Brockhausen.
Keywords for this news article include: Canada, Ontario, Kingston, Therapeutics, Transferases, Enzymes and Coenzymes, North and Central America
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