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: 8170275
• 负责人: STEWART TURLEY
• 金额: $ 0.34万
• 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/8170275
• 关键词: Affinity; African Trypanosomiasis; Amino Acyl-tRNA Synthetases; Antibodies; Architecture; Biogenesis; Characteristics; Child; Cholera; Cholera Toxin; Communicable Diseases; Computer Retrieval of Information on Scientific Projects Database; Development; Diarrhea; Disease; Drug Delivery Systems; Funding; Glycosome; Grant; Growth; Institution; Laboratories; Leishmaniasis; Malaria; Membrane; Organelles; Parasites; Pharmacologic Substance; Property; Proteins; Protozoa; RNA Editing; Research; Research Personnel; Resources; Source; Structure; System; Trypanosoma; United States National Institutes of Health; Vibrio cholerae; base; inhibitor/antagonist; insertion/deletion mutation; interest; pathogen

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 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。 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。一个特殊的特征 实验室将研究蛋白质，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。