Project Details
Description
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.
Status | Finished |
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Effective start/end date | 1/10/05 → 15/01/09 |
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