STRUCTURAL STUDIES OF VARIOUS MACROMOLECULES

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 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。我们确定了NEP1的结构，这是一种假尿苷甲基转移酶，负责核糖体小亚基解码区附近的高度修饰碱基的甲基化，与底物类似物RNA结合。因此，我们提供了催化活性和特异性的结构基础。NEP1也是导致人类Bowen-Conradi综合征的突变位点，这是一种罕见的遗传病，最终导致儿童死亡。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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 Nep1, a pseudouridine methyltransferase responsible for methylation of the hypermodified base near the decoding region of the ribosome's small subunit, bound to substrate analog RNA. We therefore provide a structural basis for catalytic activity and specificity. Nep1 is also the site of a mutation that cause Bowen-Conradi Syndrome in humans, a rare genetic disease resulting ultimately in childhood lethality.