KENDALL NETTLES PRT TIME

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。 这项研究的重点是核激素蛋白质家族。核激素受体蛋白是配体诱导的转录因子。核激素受体与多种人类疾病有关，包括癌症、肝病、肥胖症和糖尿病。具体地说，我们正在研究雌激素受体α(ERAlpha LBD)和过氧化物酶体增殖物激活受体γ(PPAR-Gamma)的配体结合域。我们的目标是更好地了解这些蛋白质的部分激活性机制，以便进行基于结构的药物设计。在实验上，我们希望表征几种与PPAR和ER结合的部分激动剂，通过X射线结晶学解析结构，剖析配体的原子水平相互作用，并将这些相互作用和诱导变构与完全激动剂和拮抗剂进行比较和对比。

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. The research focuses on the nuclear hormone family of proteins. Nuclear hormone receptor proteins are ligand inducible transcription factors. Nuclear hormone receptors are involved in several human diseases including cancer, liver disease, obesity, and diabetes. Specifically, we are working with the ligand binding domains of estrogen receptor alpha (ERalpha LBD) and peroxisome proliferator activated receptor gamma (PPAR-gamma). Our goal is to acquire a better understanding of the partial agonism mechanism of these proteins in order to carry out structure based drug design. Experimentally, we desire to characterize several partial agonists bound to PPAR and ER, solve the structures by x-ray crystallography, dissect the atomic level interactions of the ligands, and compare and contrast these interactions and induced allostery with full agonists and antagonists.