STRUCTURAL STUDIES OF VARIOUS MACROMOLECULES

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。 我们已经收集了数据，并确定了几个大分子的结构，这些大分子在不同方面对人类健康很重要。我们测定了有和没有结合底物的小鼠碘酪氨酸脱氢酶(IYD)的结构，即二碘酪氨酸和单碘酪氨酸。这种结构对这种蛋白质的先天突变引起的人类甲状腺功能减退有重要意义。我们还确定了结核分枝杆菌药物靶点的结构，即依赖谷氨酰胺的NAD+合成酶。这是这类酶的第一个结构，它揭示了这种酶的几个特征，这是没有先例的。我们还确定了连接和非连接形式的MPH(R)的结构，这是一种红霉素结合的细菌抑制物，将用于更特定的大环内酯类传感器分子的生物工程。

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 collected data and determined the structures of several macromolecules that are important in various ways to human health. We determined the structure of the mouse iodotyrosine dehaogenase (IYD) with and without bound substrates, di-iodotyrosine and mono-iodotyrosine. This structure has important implications for human hypothyroidisms caused by congenital mutations in this protein. We also determined the structure of an M.tuberculosis drug target, a glutamine dependent NAD+ synthetase. This was the first structure of this class of enzymes, and it revealed several features of the enzyme for which there is no precedence. We also determined the structures of the liganded and unliganded forms of Mph(R), an erythromycin-binding bacterial repressor, which will be used for the bioengineering of more specific macrolide sensor molecules.