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Title: Structural glycobiology by NMR and molecular modelling : ligand recognition by the carbohydrate active proteins LYVE-1, SseK1/2 and PsLBP
Author: Walpole, Samuel J.
ISNI:       0000 0004 7973 2158
Awarding Body: University of East Anglia
Current Institution: University of East Anglia
Date of Award: 2019
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The term carbohydrate-active protein (CAP) encompasses the group of proteins that either act as carbohydrate receptors (e.g. lectins) or enzymatically catalyse reactions involving carbohydrates as at least one of their substrates (e.g. glycosyltransferases). The fundamental importance of CAPs has only been realised over the past few decades, with carbohydrates playing a profound role in cellular signalling, adhesion and migration. Furthermore, carbohydrates are routinely used by pathogens in immune evasion and to modify host function, and changes in glycosylation patterns are associated with a range of disease states, including cancer and inflammation. However, the study of CAP-carbohydrate interactions has been challenging, in part due to the inherently low affinity of many CAP-carbohydrate interactions that precluded detection by many techniques and make it difficult to obtained experimentally derived structures of their complexes. Fortunately, STD NMR spectroscopy is ideally suited to detecting weak interactions of this nature and provides structural information about the interaction through ligand epitope mapping. Furthermore, quantitative analysis of STD intensities allows three-dimensional models of the validated in the solution state, whether these models be derived from experiment or molecular modelling. Within this thesis, a combination of STD NMR spectroscopy and molecular modelling has been used to unravel structural and dynamic detail of CAP-ligand interactions in three biologically or industrially relevant systems - (1) CD44/LYVE-1 which may play a role in cell trafficking across the lymphatics in cancer; (2) PsLBP which may lead to new developments in the field of enzymatic carbohydrate synthesis; (3) SseK1/2 which exhibit a novel enzymatic mechanism involving glycosylation of arginine residues and may be involved in Salmonella virulence.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available