Abstract
Nuclear magnetic resonance (NMR) spectroscopy is one of the most utilized and informative analytical techniques for investigating glycosaminoglycan (GAG)-protein complexes. NMR methods that are commonly applied to GAG-protein systems include chemical shift perturbation, saturation transfer difference, and transferred nuclear Overhauser effect. Although these NMR methods have revealed valuable insight into the protein-GAG complexes, elucidating high-resolution structural and dynamic information of these often transient interactions remains challenging. In addition, preparation of structurally homogeneous and isotopically enriched GAG ligands for structural investigations continues to be laborious. As a result, understanding of the structure-activity relationship of GAGs is still primitive. To overcome these deficiencies, several innovative NMR techniques have been developed lately. Here, we review some of the commonly used techniques along with more novel methods such as waterLOGSY and experiments to examine structure and dynamic of lysine and arginine side chains to identify GAG-binding sites. We will also present the latest technology that is used to produce isotopically enriched as well as paramagnetically tagged GAG ligands. Recent results that were obtained from solid-state NMR of amyloid’s interaction with GAG are also presented together with a brief discussion on computer assisted modeling of GAG-protein complexes using sparse experimental data.
Highlights
Glycosaminoglycans (GAGs) are linear, anionic, high molecular weight (MW) polysaccharides that are composed of repeating disaccharide building blocks of alternating hexosamine and uronic acid/galactose units (Table 1, Figure 1)
Water-ligand observed via gradient spectroscopy is an experiment whose mechanism is akin to Saturation transfer difference (STD) and transferred nuclear Overhauser effect (trNOE), but it is focused on identifying interactions between water and biomacromolecules [32]
The understanding of the resultant GAG-protein complexes at the atomic level is level is necessary better comprehend the underlying mechanisms that arein involved in these necessary to better to comprehend the underlying mechanisms that are involved these events andevents makes anddesign makesof the design of targeting new drugs targeting these proteins possible
Summary
Glycosaminoglycans (GAGs) are linear, anionic, high molecular weight (MW) polysaccharides that are composed of repeating disaccharide building blocks of alternating hexosamine and uronic acid/galactose units (Table 1, Figure 1). Among all glycoconjugates in the glycocalix, GAGs are likely to be the most important player of the extracellular matrix in terms of protein interaction and regulation. This is because of two essential characteristics of these sulfated heteropolysaccharides: (i) they are ubiquitous to all eukaryotic cells; and, (ii) their highly complex structure gives rise to unique motifs that may have specific interactions with proteins. The potential GAG-binding site(s) in GAG-binding proteins; and, (iii) understand how GAG-induced changes in protein oligomerization and conformation regulate physiological activity. N-acetylgalactosamine; GlcA2S, N,6-di-sulfated glucosamine; IdoA2S, 2-sulfated iduronic acid; GalNAc, GalNAc4S, glucuronic acid; GalNAc4S6S, 4,6-di-sulfated galactosamine; Gal, galactose; GlcNAc6S, 6-sulfated.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
