EAPSI: Development of a Powerful Protein Analysis Toolbox to Study Carbohydrate and Protein Interactions

碳水化合物和蛋白质的相互作用在生物事件中起着重要的作用。该项目将研究不同类型的酶α-L-岩藻糖苷酶的功能，该酶与含有L-岩藻糖的碳水化合物分子相互作用。L-岩藻糖是天然丰富的，并在人乳低聚糖中发现。在人类中，α-L-岩藻糖苷酶的缺乏可引起一种称为岩藻糖苷症的罕见常染色体隐性疾病，临床研究结果表明，其异常水平可能与其他罕见疾病有关。本计画将以多重碳水化合物结构为探针，探讨α-L-岩藻糖苷酶的活性。该项目的结果将提供关于α-L-岩藻糖苷酶与不同类型的碳水化合物分子之间的结构-活性关系的见解。该工具箱将进一步有利于表征新发现的α-L-岩藻糖苷酶。这项研究工作将与台湾中央研究院碳水化合物化学领域的杰出科学家林俊宏教授一起完成。林教授的研究小组已经做了大量的研究工作，研究α-L-岩藻糖苷酶，这次合作是一个宝贵的机会，了解这一研究领域的进一步方面。本计画将开发一套分子探针工具箱，以研究α-L-岩藻糖苷酶的催化活性。α-L-岩藻糖苷酶是一种重要的蛋白质，可以从碳水化合物结构中切割L-岩藻糖，一种丰富的糖分子。L-岩藻糖键可以从一种碳水化合物结构到另一种碳水化合物结构而变化。α-L-岩藻糖苷酶的缺乏或异常水平与几种医学疾病有关，包括岩藻糖苷沉积症、胃癌和囊性纤维化等。然而，α-L-岩藻糖苷酶的作用还不清楚。根据该项目的计划，将使用分子探针测试合作者小组的α-L-岩藻糖苷酶，这将允许研究蛋白质的催化功能。此外，发现对一种特定类型的L-岩藻糖键具有催化活性的α-L-岩藻糖苷酶将是有用的，因为它可以用作分析复杂碳水化合物结构的工具。该奖项属于东亚和太平洋夏季研究所计划，支持美国研究生的夏季研究，由NSF和台湾科技部共同资助。

Carbohydrate and protein interactions play important roles in biological events. This project will study functionalities of different types of the enzyme alpha-L-fucosidase, which interact with carbohydrate molecules containing L-fucose. L-fucose is naturally abundant, and found in human milk oligosaccharides. In humans, deficiency of alpha-L-fucosidase can give rise to a rare autosomal recessive disorder called fucosidosis, and clinical findings indicate that abnormal levels of it can be potentially associated with other rare diseases. This project will investigate alpha-L-fucosidase activities by using multiple carbohydrate structures as probes. The results from this project will provide insights about the structure-activity relationship between alpha-L-fucosidases and different types of carbohydrate molecules. This toolbox will be further beneficial to characterizing newly discovered alpha-L-fucosidases. This research work will be done with Professor Chun-Hung Lin, a distinguished scientist in the field of carbohydrate chemistry, at Academia Sinica Research Institute of Taiwan. Professor Lin's group has done extensive research work to study alpha-L-fucosidases and this collaboration is an invaluable opportunity to learn further aspects of this research area. This project will develop a toolbox of molecular probes to study alpha-L-fucosidase catalytic activities. Alpha-L-fucosidase is an important protein that can cleave L-fucose, an abundant sugar molecule, from carbohydrate structures. The L-fucose linkages may vary from one carbohydrate structure to another. Deficiency or abnormal levels of alpha-L-fucosidase is related to several medical conditions including fucosidosis, carcinoma of the stomach, and cystic fibrosis etc. However, the roles of alpha-L-fucosidases are not well understood. Under the plan for this project, alpha-L-fucosidases from collaborator's group will be tested with the molecular probes which will allow to study catalytic function(s) of the proteins. Additionally, discovery of alpha-L-fucosidases that are catalytically active toward one specific type of L-fucose linkage will be useful as it can be used as a tool to analyze complex carbohydrate structures.This award under the East Asia and Pacific Summer Institutes program supports summer research by a U.S. graduate student and is jointly funded by NSF and the Ministry of Science and Technology of Taiwan.