Complex carbohydrates or glycans are involved in almost every physiological or pathological process. Advances in understanding the biological roles played by glycans, along with the factors that influence or alter their functions will provid important avenues for the development of new therapeutics, and diagnostics. In recognition of opportunities to advance the impact of glycoscience on human health, we have assembled a team of five senior investigators that will work cooperatively on three related research projects to exploit unique capabilities of a Core to produce recombinant mammalian glycosyltransferases. The research projects will 1) study biochemical and structural aspects of glycosyltransferase to define their acceptor specificities at a molecular and structural level 2) exploit the enzymes in a novel chemoenzymatic approach to provide glycans for structure activity relationship studies, aid in the development of the next generation of glycan microarray and as analytical standards;3) develop sugar nucleotide donors modified by a chemical reporters to label subsets of glycoconjugates for visualization, capture and identification of glycans in cellular models of disease. The three projects have high synergy. Each requires a relatively large panel of glycosyltransferases that will be produced by a core. In addition, they will generate reciprocal knowledge and resources. Project 1 and 3 will perform complementary studies to uncover glycosyl acceptor specificities of glycosyltransferases. Information about glycosyl acceptor specificities of glycosyltransferases will be employed by Project 2 to prepare glycans that otherwise are not accessible by chemo-enzymatic synthesis. Project 2 will generate synthetic glycans that will be employed by Project 1 for in depth studies of glycosyl acceptor specificities. Structural studies by Project 1 will provide important information for project to design of sugar nucleotide donors modified with a chemical reporter for cellular studies in the context of human disease.

Public Health Relevance

Glycans play key roles in almost every biological process and are involved in every major disease. In recognition of opportunities to advance the impact of glycoscience on human health, this program project will study important aspect of the enzymes that biosynthesize these important biopolymers. The enzymes will also be employed to synthesize glycans of biomedical importance and used to monitor glycan trafficking and analysis in the context of human disease.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Program Projects (P01)
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Special Emphasis Panel (ZRG1)
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Marino, Pamela
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University of Georgia
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United States
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Urbanowicz, Breeanna R; Bharadwaj, Vivek S; Alahuhta, Markus et al. (2017) Structural, mutagenic and in silico studies of xyloglucan fucosylation in Arabidopsis thaliana suggest a water-mediated mechanism. Plant J 91:931-949
Aarnio-Peterson, Megan; Zhao, Peng; Yu, Seok-Ho et al. (2017) Altered Met receptor phosphorylation and LRP1-mediated uptake in cells lacking carbohydrate-dependent lysosomal targeting. J Biol Chem 292:15094-15104
Capicciotti, Chantelle J; Zong, Chengli; Sheikh, M Osman et al. (2017) Cell-Surface Glyco-Engineering by Exogenous Enzymatic Transfer Using a Bifunctional CMP-Neu5Ac Derivative. J Am Chem Soc 139:13342-13348
Hanes, Melinda S; Moremen, Kelley W; Cummings, Richard D (2017) Biochemical characterization of functional domains of the chaperone Cosmc. PLoS One 12:e0180242
Benedetti, Elisa; Pu?i?-Bakovi?, Maja; Keser, Toma et al. (2017) Network inference from glycoproteomics data reveals new reactions in the IgG glycosylation pathway. Nat Commun 8:1483
Sheikh, M Osman; Halmo, Stephanie M; Patel, Sneha et al. (2017) Rapid screening of sugar-nucleotide donor specificities of putative glycosyltransferases. Glycobiology 27:206-212
Liu, Lin; Prudden, Anthony R; Bosman, Gerlof P et al. (2017) Improved isolation and characterization procedure of sialylglycopeptide from egg yolk powder. Carbohydr Res 452:122-128
Halmo, Stephanie M; Singh, Danish; Patel, Sneha et al. (2017) Protein O-Linked Mannose ?-1,4-N-Acetylglucosaminyl-transferase 2 (POMGNT2) Is a Gatekeeper Enzyme for Functional Glycosylation of ?-Dystroglycan. J Biol Chem 292:2101-2109
Ding, Ning; Li, Xiuru; Chinoy, Zoeisha S et al. (2017) Synthesis of a Glycosylphosphatidylinositol Anchor Derived from Leishmania donovani That Can Be Functionalized by Cu-Catalyzed Azide-Alkyne Cycloadditions. Org Lett 19:3827-3830
Prudden, Anthony R; Liu, Lin; Capicciotti, Chantelle J et al. (2017) Synthesis of asymmetrical multiantennary human milk oligosaccharides. Proc Natl Acad Sci U S A 114:6954-6959

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