FWF - Archetypische Glykosylt - Structure and function of archetypal glycosyltransferases

    Project: Research project

    Project Details


    Simple and complex carbohydrates have been described as 'the last frontier of molecular and cell biology'. The
    carbohydrates, or often 'the sugars', are biomolecules characterised by enormous structural complexity and
    functional diversity. To a wider public, they are known mainly because they provide a major caloric portion of the
    human diet and sometimes impart a sweet taste to the product. However, physiological roles in which
    carbohydrates act as a 'cellular language' have been unveiled and rely on the huge coding potential of the individual
    monosaccharides that constitute the functional structure. Among the plethora of carbohydrate-active enzymes, those
    which can catalyse the formation of specific linkages between the monosaccharide building blocks to yield
    oligosaccharides are especially challenging. This group of enzymes, functionally classified as 'the
    glycosyltransferases' (GTs), is large, and its members differ in respect to both amino acid sequence and threedimensional
    structure, partly reflecting the complexity of the reaction products of their catalytic action. Obviously,
    a very well-defined orchestration of the action of different GTs in a place and time-dependent context is required
    to achieve a tight regulation of carbohydrate-mediated cellular responses at all levels of metabolism. In order to
    harness fully the newly bequeathed genomic resource in the form of a myriad of open-reading frames whose
    translation products that are likely involved in oligosaccharide synthesis, modification and turnover, we need to
    understand better how GT sequences relate to enzyme structure, mechanism, and specificity. The project aims at
    unraveling some "sweet secrets" of GT structure-function relationships by focusing on a representative enzyme
    group within the GT class: the phosphorylases. We will use the genome of the archaeon Sulfolobus solfataricus as
    resource of novel and seemingly archetypal variants of glycogen phosphorylase and trehalose phosphorylase, two
    important GTs of energy-related carbohydrate metabolism. The archaeal enzymes and selected mutants thereof will
    be examined through detailed biochemical and mechanistic characterisation, and their properties compared with
    homologues seen in other organisms and cell types. Through this process, means for extrapolation of molecular
    information to other sequence-related GTs are provided and strategies for the utilisation of the glycogenomic
    resource inspired.
    Effective start/end date1/10/0515/01/09


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