BOUND LIGAND GEOMETRIES FOR THE CANCER RELATED GLYCOSYLTRANSFERASE, GNTV

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。细胞表面寡糖的异常补充与癌细胞的增殖和转移有关。在负责合成这些碳水化合物的蛋白质中，有糖基转移酶，如N-乙酰氨基葡萄糖转移酶，GnTV。由于小鼠敲除这种蛋白已被证明可以抑制肿瘤转移，因此它已成为开发其作用的特定抑制剂的目标。本项目旨在研究GnTV及其结合配体的结构特征。特别是，正在开发高灵敏的核磁共振技术，包括使用微线圈和低温流动探针，以收集碳水化合物给体和受体结合几何的结构信息，为抑制剂设计提供基础。

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. An abnormal complement of cell-surface oligosaccharides is known to correlate with proliferation and metastasis of cancer cells. Among the proteins responsible for the synthesis of these carbohydrates are glycosyltransferases such as the N-acetylglucosamine transferase, GnTV. Since mouse knock-outs of this protein have been shown to inhibit metastasis, it has become a target for the development of specific inhibitors of its action. This project is directed at the structural characterization of GnTV and its bound ligands. In particular, highly sensitive NMR technology, including the use of micro-coil and cryogenic flow probes, is being developed to gather structural information on the bound geometries of carbohydrate donors and acceptors to provide a basis for inhibitor design.