Structural and functional studies of enzymes involved in glycosaminoglycan synthesis and degradation

这项建议旨在对参与糖胺多聚糖(GAG)合成和降解的酶的结构和功能进行表征。GAG是一种带负电荷的线性多糖，对于提供对结缔组织的弹性、生长因子和其他蛋白质的储存、参与组织修复和通过受体传递信号至关重要。GAG的存在通常与高等生物有关；然而，它们并不是真核生物所特有的。几种特殊的微生物也会产生这些聚合物的非硫酸盐形式。哺乳动物的胃通过水解酶的作用迅速周转。细菌进化出使用裂解机制来降解GAG的酶，即多糖裂解酶。这些酶通过降解表面多糖或将GaGs用作食物来源来帮助细菌进入哺乳动物细胞。

This proposal aims at a structural and functional characterization of enzymes involved in synthesis and degradation of glycosaminoglycans (GAGs). GAGs are negatively charged linear polysaccharides that are essential for providing resilience to connective tissues, storage of growth factors and other proteins, participate in tissue repair and signaling through receptors. The presence of GAGs is usually associated with higher organisms; however, they are not unique to eukaryotes. Several specialized microorganisms also produce unsulfated forms of these polymers. Mammalian GAGs undergo rapid turnover through action of hydrolases. Bacteria evolved enzymes that use a lytic mechanism to degrade GAGs, namely polysaccharide lyases. These enzymes help bacteria to gain access to mammalian cells by degrading the surface polysaccharides or to utilize GAGs as a food source.