STRUCTURAL STUDIES OF HUMAN NTP-BINDING PROTEINS

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。 NTP结合蛋白，如激酶和ATPase，在原核生物和真核生物中都是重要的生物活性效应因子。因此，它们也是重要的药物靶点。在下面的提案中，我们建议对几个关键的人类NTP结合蛋白进行结构研究，以进一步阐明它们的功能机制，并将这些蛋白整合到基于结构的交互药物设计周期中。我们的目标是对多个项目进行结构研究。这些实验产生的结构结果将用于基于结构的迭代药物设计计划，旨在开发针对黑色素瘤、乳腺癌和小细胞肺癌等侵袭性极强的人类癌症的疗法。在这样的药物设计周期中，快速设计和优化先导化合物是有责任及时获得同步加速器来源，以产生所需的结构数据。

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. NTP-binding proteins, such as kinases and ATPases, are important effectors of biological activity in both prokaryotes and eukaryotes. Therefore, they are also important drug targets. In the following proposal we propose to perform structural studies on several key human NTP-binding proteins to further elucidate their mechanism of function, as well as to integrate these proteins into an interactive structure-based drug design cycle. Our goal is to perform structural studies on multiple projects. The structural results generated by these experiments will be used in an iterative structure-based drug design program aimed at developing therapeutics against very aggressive human cancers such as melanoma, breast cancer, and small-cell lung cancer. Rapid design and optimization of the lead compounds in such a drug design cycle is incumbent on timely access to synchrotron sources for the generation of the needed structural data.