CRYSTALLOGRAPHIC STUDIES OF CELL MIGRATION AND HOST-PATHOGEN INTERACTIONS

细胞迁移和宿主-病原体相互作用的晶体学研究

• 批准号: 8169953
• 负责人: ROBERT Colin LIDDINGTON
• 金额: $ 0.13万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169953
• 关键词: Antibodies; Area; Categories; Cells; Centers for Disease Control and Prevention (U.S.); Complex; Computer Retrieval of Information on Scientific Projects Database; Data; Data Collection; Drug Design; Funding; Grant; Institution; International; Journals; Laboratories; Lipids; Paper; Phase; Proteins; Publishing; Research; Research Personnel; Resolution; Resources; Source; Structure; Synchrotrons; Toxin; United States National Institutes of Health; Virulence Factors; Work; anthrax lethal factor; cell motility; inhibitor/antagonist; novel; pathogen; small molecule

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. The SSRL continues to be our first choice for access to macromolecular synchrotron beam-lines. Our principal needs are tunability for MAD phasing, high brightness for data collection from large unit cells, and relatively high-throughput data collection for toxin-inhibitor complexes. Our work covers a broad range of protein targets, with an emphasis in two areas: (1) key virulence factors from CDC Category A-C pathogens, and their complexes with host proteins and antibodies, as well as small molecule inhibitors of these interactions to facilitate drug design; and (2) the major proteins and their protein-protein and protein-lipid interactions that control cell migration. Some of these proteins are large, and their necessarily large unit cells demand a high brightness source for high resolution data collection. For proteins in the medium-sized range, such as anthrax lethal factor, SR makes the key difference for collecting data of sufficient resolution for the purpose of rational drug design. In other cases, a tunable source with reasonable brightness is sufficient for ab initio phasing. Over the past 6 years, data collected at the SSRL have been critical for the structure determination of more than 20 novel crystal structures from this laboratory, leading to 23 papers published in international journals.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 SSRL仍然是我们进入大分子同步束线的首选。我们的主要需求是可调性，用于疯狂的相位，大型单位细胞收集数据收集的高亮度以及毒素抑制剂复合物的相对高通量数据收集。我们的工作涵盖了广泛的蛋白质靶标，重点是两个领域：（1）CDC类A-C类病原体的关键毒力因子及其与宿主蛋白和抗体的复合物以及这些相互作用的小分子抑制剂的复合物，以促进药物设计； （2）控制细胞迁移的主要蛋白质及其蛋白质 - 蛋白质蛋白和蛋白 - 脂质相互作用。这些蛋白质中的一些很大，它们的一定是大型单元需要高分辨率数据收集的高亮度来源。对于中型范围内的蛋白质（例如炭疽致死因子），SR为收集足够分辨率的数据而言是为了理性药物设计的关键区别。在其他情况下，具有合理亮度的可调源足以从头算。在过去的6年中，在SSRL收集的数据对于确定该实验室的20多种新型晶体结构的结构至关重要，导致在国际期刊上发表了23篇论文。