STRUCTURAL STUDIES OF VARIOUS MACROMOLECULES

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们已经收集了数据，并确定了几种对人类健康具有重要意义的大分子的结构。我们确定了小鼠碘酪氨酸脱haogenase（IYD）的结构，有和没有结合底物，二碘酪氨酸和单碘酪氨酸。这种结构对于由这种蛋白质的先天性突变引起的人类甲状腺功能减退症具有重要意义。我们还确定了结核分枝杆菌药物靶标的结构，即谷氨酰胺依赖性NAD+合成酶。这是这类酶的第一个结构，它揭示了酶的几个特征，这些特征是没有先例的。 我们还确定了Mph（R）的配体和非配体形式的结构，Mph（R）是一种红霉素结合细菌阻遏物，将用于更特异性的大环内酯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.