CRYSTALLOGRAPHIC STUDIES OF KEY PROTEINS FROM GLOBAL INFECTIOUS DISEASES

全球传染病关键蛋白质的晶体学研究

• 批准号: 8362274
• 负责人: STEWART TURLEY
• 金额: $ 0.22万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362274
• 关键词: Affinity; African Trypanosomiasis; Amino Acyl-tRNA Synthetases; Antibodies; Architecture; Biogenesis; Characteristics; Child; Cholera; Cholera Toxin; Communicable Diseases; Development; Diarrhea; Disease; Drug Delivery Systems; Funding; Glycosome; Grant; Growth; Laboratories; Leishmaniasis; Malaria; Membrane; National Center for Research Resources; Organelles; Parasites; Pharmacologic Substance; Principal Investigator; Property; Proteins; Protozoa; RNA Editing; Radiation; Research; Research Infrastructure; Resources; Source; Structure; System; Trypanosoma; United States National Institutes of Health; Vibrio cholerae; base; cost; inhibitor/antagonist; insertion/deletion mutation; interest; pathogen; structural biology

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 Hol laboratory is focused on proteins from major global pathogens that are promising targets for the development of much-needed new pharmaceuticals to treat such diseases as malaria, sleeping sickness, leishmaniasis, children?s diarrhea and cholera. A special characteristic of the laboratory is to study proteins and in particular multi-proteins assemblies that are, by themselves, extremely interesting with respect to architecture, function and properties. On the basis of the structures obtained we also aim to obtain high affinity inhibitors. As a result we are investigating three multi-protein assemblies, including (i) the Type 2 Secretion System which exports cholera toxin across the outer membrane of Vibrio cholerae, (ii) the unique U-insertion/deletion RNA editing system in Trypanosomatids, and (iii) the invasion machinery of the malaria parasite. In addition we are studying peroxins, proteins essential for the biogenesis of the unique glycosome organelles in trypanosomes, and carefully selected tRNA synthetases from a variety of pathogenic protozoa which are exciting drug targets. A new development in the lab is the use of single-domain antibodies from camelids, called ?nanobodies?, which in many cases greatly accelerate crystal growth, and also assist in structure determination.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 HOL实验室的重点是来自主要全球病原体的蛋白质，这些蛋白质是开发急需的新药物的有希望的靶标，以治疗诸如疟疾，睡眠疾病，利什曼病，儿童腹泻和霍乱等疾病。实验室的一个特征是研究蛋白质，特别是在建筑，功能和特性方面非常有趣的多蛋白质组件。根据获得的结构，我们还旨在获得高亲和力抑制剂。结果，我们正在研究三个多蛋白质组件，包括（i）2型分泌系统，该系统将霍乱毒素导出了弧形霍乱的外膜，（ii）在底帕氏剂中的独特的U插入/缺失RNA RNA编辑系统，以及（III）的射击机械。此外，我们正在研究过氧蛋白，蛋白对于锥虫中独特的糖体细胞器的生物发生至关重要，以及来自各种致病原生动物的精心选择的tRNA合成酶，这是令人兴奋的药物靶标。实验室中的新开发是使用来自骆驼的单域抗体，称为纳米生物，在许多情况下，哪些抗体大大加速了晶体生长，也有助于确定结构。