Dissection of alpha mannosidases: from reaction coordinate to inhibition

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Sugars are more than just food. Sugars coat all our cells and the cells of our pathogens. The communication between cells, both healthy and pathogenic, both normal and tumour is governed by sugars. Sugars are 'the language of the cell'. The chemical factories that make, modify and tune sugars are called 'enzymes'. The control and organisation of these enzymatic machines is central to the healthy organism and, conversely, their subversion leads to changes in cell growth, auto immune disease and cancers. An unusual sugar, called mannose, is of particular interest to scientists as its chemistry is very difficult (its crowded centres make reactions difficult) and because the enzymes involved in its modification are both highly unusual and implicated in cell division and disease. The aim of this BBSRC grant is to study enzymes involved in mannose chemistry, to dissect them at the three-dimensional level and then to use cunning chemistry to both study their reaction and inspire and analyse inhibitors that should lead to chemical probes of healthy cells and potential therapeutic agents.