STRUCTURAL ANALYSES OF HUMAN ESTROGEN RECEPTOR IN COMPLEX WITH EFFECTOR/REGUL

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。 这项建议是我们正在进行的结构研究的一部分，目的是表征多结构域的人类雌激素受体(HER)，它与调节/效应蛋白和潜在的治疗性小分子的相互作用。过去，我们在APS收集了HER配体结合域(LBD)与其单体(PDB代码：2OCF)的第一次蛋白质-蛋白质相互作用的数据，也收集了LBD与各种配体(最后一次运行中与estetrol，PDB代码：3L03)的络合物的数据。我们已经得到了新的配体与LBD的配合物的晶体，以及HER的其他结构域的晶体。此外，我们还有衍射性很好的梅宁晶体，这是一种多内分泌肿瘤蛋白，已被证明与HER形成复合体。我们要求光束时间来筛选这些晶体，评估它们的衍射质量，并收集那些衍射良好的晶体的数据。

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. This proposal is part of our ongoing structural studies aimed at the characterization of the multi-domain human Estrogen Receptor (hER), its interaction with regulator/effector proteins and potential therapeutic small molecules. In the past we have collected data at the APS on the first protein-protein interaction of the hER ligand binding domain (LBD), complexed with its monobody (pdb code: 2OCF) and also on complexes of LBD with various ligands (with Estetrol in the last run, pdb code: 3L03). We have obtained crystals of new ligand complexes with the LBD, as well as crystals of the other domains of hER. In addition, we have well-diffracting crystals of Menin, multiple endocrine neoplasia protein, that has been shown to form a complex with the hER. We request beam time to screen these crystals, evaluate them for diffraction quality and collect data on those that diffract well.