X-RAY CRYSTALLOGRAPHY AND PROTEIN EXPRESSION

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。 Loll实验室的研究围绕着分子结构展开。我们所有项目的基本目标是在分子水平上了解重要的生物学过程。我们的主要工具是X射线结晶学；我们还在蛋白质表达、蛋白质生物化学、光谱学和酶学方面投入了大量精力来支持结构工作。具体感兴趣的领域包括： *大型天然产品抗生素。Loll和学生正在应用结构、计算和生物物理方法来加深我们对万古霉素、雷莫拉宁、酪氨酸和杆菌肽等抗生素如何发挥作用的理解。他们希望利用这些信息来设计对抗抗生素耐药性的新药。 *毒品行动的结构性基础。我们感兴趣的是在结构水平上探索药物与其蛋白质靶标之间的相互作用。目前，他们正在研究全身麻醉剂与模型蛋白质靶标的结合，着眼于阐明控制麻醉剂识别的结构决定因素。 *约瑟芬蛋白的去泛素化作用。Aaxin-3和其他约瑟芬蛋白催化多聚泛素链的降解，调节控制蛋白质分解和运输的信号。他们正在使用结构和生化方法来研究这些酶的功能。 *聚谷氨酰胺病的分子机制。我们正在研究神经退行性马查多-约瑟夫病的病原体ataxin-3，使用结构、超微结构、生化和生物物理方法来了解聚谷氨酰胺束的扩张是如何导致蛋白质错误折叠、纤维形成和神经元死亡的。 *膜蛋白的结构生物学。发生在活细胞中的许多最吸引人和最关键的过程都是由完整的膜蛋白调节的。Loll实验室正在研究一些不同的膜结合酶、受体和转运蛋白；此外，大量的工作集中在这些分子的结晶方法的开发上。

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. Research in the Loll lab revolves around molecular structure. The underlying goal for all our projects is to understand biologically important processes at the molecular level. Our principal tool is X-ray crystallography; we also devote much energy to protein expression, protein biochemistry, spectroscopy, and enzymology to support the structural efforts. Specific areas of interest include: * Large natural product antibiotics. Loll and students are applying structural, computational, and biophysical methods to deepen our understanding of how antibiotics like vancomycin, ramoplanin, tyrocidine, and bacitracin function. They hope to use this information to design novel drugs to combat antibiotic resistance. * The structural basis of drug action. We are interested in probing the interactions between drugs and their protein targets at the structural level. Currently, they are examining the binding of general anesthetics to model protein targets, with an eye toward elucidating the structural determinants that control anesthetic recognition. * Deubiquitylation by Josephin proteins. Ataxin-3 and other Josephin proteins catalyze the degradation of poly-ubiquitin chains, modulating signals controlling protein breakdown and trafficking. They are using structural and biochemical approaches to study the function of these enzymes. * The molecular mechanism of polyglutamine disease. We are studying ataxin-3, the causative agent of the neurodegenerative Machado-Joseph disease, using structural, ultrastructural, biochemical, and biophysical methods to understand how expansion of polyglutamine tracts leads to protein misfolding, fibril formation, and neuronal death. * The structural biology of membrane proteins. Many of the most fascinating and crucial processes which occur in living cells are modulated by integral membrane proteins. The Loll lab is studying a number of different membrane-bound enzymes, receptors, and transport proteins; in addition, a substantial effort focuses on the development of crystallization methodologies for these molecules.