Dissection of alpha mannosidases: from reaction coordinate to inhibition

糖不仅仅是食物。糖类覆盖着我们所有的细胞和病原体的细胞。细胞之间的通讯，无论是健康的还是致病的，正常的和肿瘤的都是由糖控制的。糖是“细胞的语言”。制造、修饰和调节糖的化工厂被称为“酶”。这些酶机器的控制和组织是健康有机体的核心，反过来，它们的颠覆会导致细胞生长、自身免疫性疾病和癌症的变化。科学家们对一种名为甘露糖的不同寻常的糖特别感兴趣，因为它的化学非常困难(其拥挤的中心使反应变得困难)，而且参与其修饰的酶既非常不寻常，又与细胞分裂和疾病有关。这笔BBSRC赠款的目的是研究参与甘露糖化学的酶，在三维水平上剖析它们，然后使用巧妙的化学来研究它们的反应，并激发和分析抑制物，这些抑制物应该导致健康细胞和潜在的治疗药物的化学探针。

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.