SAD/MAD/MIR PHASING WITH CRYSTALS OF TERMINAL URIDYLYL TRANSFERASE 4

末端尿苷酰转移酶 4 晶体的 SAD/MAD/MIR 定相

• 批准号: 7721921
• 负责人: JASON STAGNO
• 金额: $ 0.46万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7721921
• 关键词: African Trypanosomiasis; Chagas Disease; Computer Retrieval of Information on Scientific Projects Database; Data Set; Disease; Drug Delivery Systems; Enzymes; Family; Funding; Grant; Human; Institution; Investigation; Leishmaniasis; Mechanics; Nucleotides; Phase; RNA; RNA Editing; Research; Research Personnel; Resources; Role; Sequence Homology; Source; Specificity; Transferase; Translations; United States National Institutes of Health; Uridine Monophosphate; base; novel; protein structure

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. TUT4, or terminal uridylyl transferase 4, is one of a family of RNA-editing enzymes found in trypanosomatids. Although it?s exact role has yet to be identified, it?s basic function, like other TUTases involves the incorporation of UMP into RNA strands that must first be edited prior to translation. Trypanosomatids are responsible for fatal diseases such as African sleeping sickness, Chagas disease, and leishmaniasis. Furthermore, no closely homologous enzymes have been found in humans, making TUTases good potential drug targets. TUT4 is currently the smallest known TUTase and contains all of the conserved functional domains, making it an attractive target for crystallographic investigation with aims such as identifying novel enzyme mechanics and how nucleotide base specificity is achieved. A native data-set has already been collected on a crystal of this enzyme. However, since there are no protein structures available with enough sequence homology, heavy-atom derivatives and are being generated to solve the phase problem. Therefore, a MAD beam line is necessary for further experimentation.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 TUT4（或末端尿苷酰转移酶 4）是锥虫中发现的 RNA 编辑酶家族之一。 虽然它的确切作用尚未确定，但它的基本功能与其他 TUTase 一样，涉及将 UMP 掺入 RNA 链，在翻译之前必须首先对 RNA 链进行编辑。 锥虫是导致非洲昏睡病、查加斯病和利什曼病等致命疾病的罪魁祸首。此外，在人类中尚未发现紧密同源的酶，这使得 TUTase 成为良好的潜在药物靶标。 TUT4 是目前已知的最小的 TUTase，包含所有保守的功能域，使其成为晶体学研究的一个有吸引力的目标，其目的包括识别新的酶机制以及如何实现核苷酸碱基特异性。已经收集了该酶晶体的原始数据集。 然而，由于没有具有足够序列同源性的蛋白质结构，因此正在生成重原子衍生物来解决相位问题。 因此，MAD 光束线对于进一步的实验是必要的。