A Guided Tour of the Structural Biology of Gaucher Disease: Acid-β-Glucosidase and Saposin C.
A Guided Tour of the Structural Biology of Gaucher Disease: Acid-β-Glucosidase and Saposin C.
复制标题
DOI：
10.4061/2011/973231
复制
发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Lieberman RL
中科院分区：
文献类型：
--
作者：
Lieberman RL
酸性-β-葡萄糖苷酶 (GCase) 和 saposin C 的突变会导致戈谢病，这是最常见的溶酶体贮积症。在过去的几年里，这些蛋白质的结构和生化信息激增，为戈谢病的生物学和发病机制提供了新的见解，并为新的治疗方向提供了机会。现在有近 20 种 GCase 晶体结构可供使用，它们来自不同的异源来源，与活性位点上的不同配体以不同的糖基化状态复合，以及一种含有普遍致病突变 N370S 的晶体结构。对于saposin C，已经解析了两个NMR 和3 个晶体结构，每个结构都有其独特的快照。本综述重点关注这些结构的细节，以突出突出的共同特征和不同特征，这些特征有助于我们目前对这种复杂的孤儿疾病的了解。
Mutations in both acid-β-glucosidase (GCase) and saposin C lead to Gaucher disease, the most common lysosomal storage disorder. The past several years have seen an explosion of structural and biochemical information for these proteins, which have provided new insight into the biology and pathogenesis of Gaucher disease, as well as opportunities for new therapeutic directions. Nearly 20 crystal structures of GCase are now available, from different heterologous sources, complexed with different ligands in the active site, in different glycosylation states, as well as one that harbors a prevalent disease-causing mutation, N370S. For saposin C, two NMR and 3 crystal structures have been solved, each with its unique snapshot. This review focuses on the details of these structures to highlight salient common and disparate features that contribute to our current state of knowledge of this complex orphan disease.