GLYCOSIDASES IN HUMAN HEALTH AND DISEASE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们一直在研究与人类健康和疾病相关的糖苷水解酶的结构和功能。高尔基体α-甘露糖苷酶II是哺乳动物N-糖基化途径的核心，是抗肿瘤转移的靶点。我们计划收集一些基于我们的结构结果(其中一些来自国际象棋数据)开发的具有新型抑制剂的络合物。麦芽糖酶是肠道淀粉消化中的一种重要酶，也是抗糖尿病药物的靶点。我们用CHESS数据解决了结构问题，现在正在收集新的抑制剂络合物，并试图提高分辨率。最后，α-葡萄糖苷酶I是蛋白质折叠“质量控制”途径中的第一个酶。这是一个新的结构，我们将收集本地数据，可能还会收集衍生(卤化物浸泡)数据。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We have been studying the structures and functions of glycoside hydrolases involved in human health and disease. Golgi alpha-mannosidase II is at the core of the mammalian N-glycosylation pathway, and is an anti-metastatic target. We plan to collect some complexes with novel inhibitors that have been developed based on our structural results (some of which were from CHESS data). Maltase glucoamylase is an important enzyme in intestinal starch digestion and a target for anti-diabetics. We solved the structure with CHESS data and are now collecting novel inhibitor complexes and attempting to improve the resolution. Finally, a-glucosidase I is the first enzyme in the protein folding `quality control` pathway. This is a new structure and we wil be collecting native data and possibly derivative (halide soak) data.