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.
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.
|Kadirvelraj, Renuka; Yang, Jeong-Yeh; Sanders, Justin H et al. (2018) Human N-acetylglucosaminyltransferase II substrate recognition uses a modular architecture that includes a convergent exosite. Proc Natl Acad Sci U S A 115:4637-4642|
|Jensen, Jacob Krüger; Busse-Wicher, Marta; Poulsen, Christian Peter et al. (2018) Identification of an algal xylan synthase indicates that there is functional orthology between algal and plant cell wall biosynthesis. New Phytol 218:1049-1060|
|Voiniciuc, C?t?lin; Engle, Kristen A; Günl, Markus et al. (2018) Identification of Key Enzymes for Pectin Synthesis in Seed Mucilage. Plant Physiol 178:1045-1064|
|Moure, Maria J; Eletsky, Alexander; Gao, Qi et al. (2018) Paramagnetic Tag for Glycosylation Sites in Glycoproteins: Structural Constraints on Heparan Sulfate Binding to Robo1. ACS Chem Biol 13:2560-2567|
|Moremen, Kelley W; Ramiah, Annapoorani; Stuart, Melissa et al. (2018) Expression system for structural and functional studies of human glycosylation enzymes. Nat Chem Biol 14:156-162|
|Yu, Seok-Ho; Zhao, Peng; Prabhakar, Pradeep K et al. (2018) Defective mucin-type glycosylation on ?-dystroglycan in COG-deficient cells increases its susceptibility to bacterial proteases. J Biol Chem 293:14534-14544|
|Liu, Lin; Prudden, Anthony R; Capicciotti, Chantelle J et al. (2018) Streamlining the chemoenzymatic synthesis of complex N-glycans by a stop and go strategy. Nat Chem :|
|Muchero, Wellington; Sondreli, Kelsey L; Chen, Jin-Gui et al. (2018) Association mapping, transcriptomics, and transient expression identify candidate genes mediating plant-pathogen interactions in a tree. Proc Natl Acad Sci U S A 115:11573-11578|
|Jiang, Hao; López-Aguilar, Aimé; Meng, Lu et al. (2018) Modulating Cell-Surface Receptor Signaling and Ion Channel Functions by In?Situ Glycan Editing. Angew Chem Int Ed Engl 57:967-971|
|Epp, Alexandra; Hobusch, Juliane; Bartsch, Yannic C et al. (2018) Sialylation of IgG antibodies inhibits IgG-mediated allergic reactions. J Allergy Clin Immunol 141:399-402.e8|
Showing the most recent 10 out of 42 publications