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: 7370685
• 负责人: JASON STAGNO
• 金额: $ 0.02万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7370685
• 关键词: SAD; MAD; MIR; PHASING; CRYSTALS

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.

该主题项目是利用NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。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。列出的机构是针对该中心的，这不是调查人员的机构。 TUT4或末端尿液转移酶4是在锥虫中发现的RNA编辑酶的家族之一。尽管它的确切作用尚未确定，但它的基本功能就像其他辅助酶一样，涉及将UMP掺入RNA链中，这些链中必须先对翻译之前进行编辑。锥虫病负责致命疾病，例如非洲睡眠疾病，chagas病和利什曼病。此外，在人类中没有发现紧密的同源酶，这使诱导酶良好的潜在药物靶标。 TUT4目前是最小的已知tutase，并包含所有配置的功能域，使其成为晶体学研究的有吸引力的目标，其目的（例如识别新型酶机制以及如何实现核丁基碱基特异性）。本机数据集已经在该酶的晶体上收集。但是，由于没有蛋白质结构具有足够的序列同源性，重大原子衍生物，并且正在生成以解决相位问题。因此，对于进一步的实验，需要疯狂的光束线。