EXCEED THE SPACE PROVIDED. A new class of nuclear magnetic resonance (NMR) experiments is applied to the characterization of structural and dynamic aspects of oligosaccharide-protein interactions that occur at cell surfaces. These interactions frequently mediate cell-cell contactsthat are important to host defense against invading organisms, to control of differentiation and activation of cells, and to recruitment of cells in events such as inflammatory response. Design of agents that can mimic or compete with natural participants in these interactions is important in combating disease. But,rational design of these reagents can only be undertaken with adequate molecular level descriptions of how key interactions occur. The long range goal of this project is providing this molecular level description. The specific approach is meant to provide a comparison of oligosaccharide structure and dynamics, in the whole range of environments over which the interactions occur; free in solution, bound to membrane, and bound to protein. NMR approaches that utilize orientational dependence as well as distance dependence of observables are uniquely suited to these investigations. Testing of this new methodology is a key component of the research. The primary systems selected for application and testing are C-type lectins and their carbohydrate ligands. These include the carbohydrate recognition domain of mannose binding protein, with its mannose or N-acetylglucosamine terminated ligands, and the carbohydrate recognition domains from a selectin, with its sialyl-Lewis' related ligands. Abnormal function of both systems relate to current health concerns. PERFORMANCE SITE ========================================Section End===========================================

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37GM033225-21
Application #
6890348
Study Section
Special Emphasis Panel (NSS)
Program Officer
Wehrle, Janna P
Project Start
1984-07-01
Project End
2009-04-30
Budget Start
2005-05-01
Budget End
2006-04-30
Support Year
21
Fiscal Year
2005
Total Cost
$354,216
Indirect Cost
Name
University of Georgia
Department
Type
Organized Research Units
DUNS #
004315578
City
Athens
State
GA
Country
United States
Zip Code
30602
Chalmers, G; Glushka, J N; Foley, B L et al. (2016) Direct NOE simulation from long MD trajectories. J Magn Reson 265:1-9
Barb, Adam W; Glushka, John N; Prestegard, James H (2011) Kinetics of Neuraminidase Action on Glycoproteins by 1D and 2D NMR. J Chem Educ 88:95-97
Barb, Adam W; Brady, Evan K; Prestegard, James H (2009) Branch-specific sialylation of IgG-Fc glycans by ST6Gal-I. Biochemistry 48:9705-7
Zhuang, Tiandi; Lee, Han-Seung; Imperiali, Barbara et al. (2008) Structure determination of a Galectin-3-carbohydrate complex using paramagnetism-based NMR constraints. Protein Sci 17:1220-31
Macnaughtan, Megan A; Tian, Fang; Liu, Shan et al. (2008) 13C-sialic acid labeling of glycans on glycoproteins using ST6Gal-I. J Am Chem Soc 130:11864-5
Wang, Xu; Weldeghiorghis, Thomas; Zhang, Guofeng et al. (2008) Solution structure of Alg13: the sugar donor subunit of a yeast N-acetylglucosamine transferase. Structure 16:965-75
Yu, Fei; Wolff, Jeremy J; Amster, I Jonathan et al. (2007) Conformational preferences of chondroitin sulfate oligomers using partially oriented NMR spectroscopy of 13C-labeled acetyl groups. J Am Chem Soc 129:13288-97
Seidel 3rd, Ronald D; Zhuang, Tiandi; Prestegard, James H (2007) Bound-state residual dipolar couplings for rapidly exchanging ligands of His-tagged proteins. J Am Chem Soc 129:4834-9
Macnaughtan, Megan A; Kamar, Maria; Alvarez-Manilla, Gerardo et al. (2007) NMR structural characterization of substrates bound to N-acetylglucosaminyltransferase V. J Mol Biol 366:1266-81
Liu, Shan; Venot, Andre; Meng, Lu et al. (2007) Spin-labeled analogs of CMP-NeuAc as NMR probes of the alpha-2,6-sialyltransferase ST6Gal I. Chem Biol 14:409-18

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