Ferrara, Maria Carmina (2013) Carbohydrate-Active enZYmes: functional and applicative aspects of glycoside hydrolases. [Tesi di dottorato]

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Abstract

Carbohydrates play an important role in a variety of biological and industrial processes. The elucidation of the structure/function relationship of glycoside hydrolases (GHs) can help us to understand their implication in various biological phenomena and to exploit their catalytic features, i. e. in pharmacological therapies or to optimize industrial processes. On the basis of these observations, this thesis work is directed to the study of GHs structure/function relationship and, besides the general introduction illustrated in chapter 1, it can be subdivided in two principal experimental sections (chapter 2 and 3). In chapter 2, the research plan was focused on the identification and biochemical characterization of novel glycosidases activities in the hyperthermophilic crenarchaeon Sulfolobus solfataricus. This study allowed to identify the first N-acetylglucosaminidase in this living domain, to increase our knowledge on the phylogeny of this class of enzymes, and to achieve additional data concerning their structural and functional features. Chapter 3 reports the structure/function study of the human lysosomal α-glucosidase, shading light on the factors responsible of its stabilization. The informations gained are exploited to identify novel pharmacological chaperones for the therapy of the lysosomal storage disorder known as Pompe disease.

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