STRUCTURE DETERMINATION OF AN INTACT BACTERIAL

完整细菌的结构测定

• 批准号: 7957310
• 负责人: SCOTT A STROBEL
• 金额: $ 6.99万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7957310
• 关键词: Active Sites; Biochemistry; Biological; Biological Process; Catalysis; Catalytic RNA; Chemicals; Communities; Computer Retrieval of Information on Scientific Projects Database; Crystallography; Experimental Designs; Funding; Goals; Grant; Group Structure; Heavy Metals; Institution; Introns; Ions; Life; Light; Metals; Nature; Organism; Peptides; Process; Protein Biosynthesis; RNA; RNA Splicing; Reaction; Research; Research Personnel; Resolution; Resources; Ribosomes; Role; Source; Structure; Synchrotrons; United States National Institutes of Health; Work; base; catalyst; inhibitor/antagonist; insight; interest; mRNA Precursor; metalloenzyme; progenitor

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. There are several classes of naturally occurring catalytic RNAs or ribozymes. The importance of understanding how this class of biocatalysts promotes their reactions became evident with the recent structure determination of the 50S ribosome, which demonstrated that protein synthesis in all living organisms occurs within an RNA active site. Ribozymes are the molecules most likely to be the progenitors of modern biological catalysts and understanding how they promote their reactions provides critical insight into enzymological function. This project focuses on the structure of the group I self-splicing intron, the first class of catalytic RNAs discovered. Structural information is necessary to understand and interpret the biological function of this class of biocatalyst. We are working toward three goals. 1. The primary aim of this project is to determine the high resolution x-ray crystal structure of an intact bacterial group I self-splicing intron. If this aim is achieved, two additional projects will be undertaken: 2. Heavy metal ions and alternative intron inhibitors will be used to structurally investigate how metal ions contribute to group I intron folding and catalysis. 3. The transition state of the phosphotransfer reaction will be structurally explored using stable mimics of the transition state geometry. These studies will provide a structural basis for more than 20 years of biochemistry. It will also provide chemical insights into the nature of RNA catalysis, particularly for an RNA metalloenzyme, an example of which has not yet been structurally analyzed. RNA catalysis is an issue of particular interest given the critical of role of RNA in several natural processes including peptide bond formation and pre-mRNA splicing. The coordinates will be made available to the scientific community for analysis and experimental design.

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。 有几类天然存在的催化RNA或核酶。 了解这类生物催化剂如何促进其反应的重要性在最近的50S核糖体的最新结构确定中变得明显，这表明所有生物中的蛋白质合成都发生在RNA活性位点中。 核酶是最有可能是现代生物催化剂的祖细胞的分子，并且了解它们如何促进其反应提供了对酶学功能的重要见解。 该项目的重点是第一类催化RNA的自剪式内含子的结构。 结构信息对于理解和解释这类生物催化剂的生物学功能是必要的。 我们正在朝着三个目标努力。 1。该项目的主要目的是确定完整细菌I组自剪接内含子的高分辨率X射线晶体结构。 如果实现了这一目标，将进行其他两个项目： 2。重金属离子和替代内含子抑制剂将用于在结构上研究金属离子如何对I组内含子折叠和催化的贡献。 3。将使用稳定的过渡状态几何形状的模拟物在结构上探索磷酸反应的过渡态。 这些研究将为20年以上的生物化学提供结构性基础。 它还将提供有关RNA催化性质的化学见解，特别是对于RNA金属酶，尚未在结构上进行结构分析。 鉴于RNA在几种自然过程中的作用（包括肽键形成和前MRNA剪接），RNA催化是特别关注的问题。 坐标将提供给科学界的分析和实验设计。