CRYSTALLOGRAPHIC STUDIES ON HUMAN DNA TOPOISOMERASE I

人类 DNA 拓扑异构酶 I 的晶体学研究

• 批准号: 7721789
• 负责人: LANCE J STEWART
• 金额: $ 0.02万
• 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/7721789
• 关键词: Antineoplastic Agents; Complex; Computer Retrieval of Information on Scientific Projects Database; DNA; DNA biosynthesis; Data Collection; Development; Enzymes; Funding; Grant; Human; Institution; Research; Research Personnel; Resources; Role; Source; Structure; Synchrotrons; Topoisomerase; Type I DNA Topoisomerases; United States National Institutes of Health; design; ds-DNA; human TOP1 protein; inhibitor/antagonist; novel

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. Human DNA topoisomerase I (topo I) is an enzyme which relaxes helical strain in double-stranded DNA. Topo I has a critical role in DNA replication. It is also an attractive target for some anti-cancer drugs which inhibit the catalytic mechanism of topo I. We have recently determined the structures of ternary complexes of topo I with its substrate DNA and anti-cancer drugs. Topo I crystals generally diffract very weakly. We request synchrotron beamtime for x-ray diffraction data collection on additional topo I complex crystals for our ongoing design and development of novel topo I inhibitors.

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。 人类 DNA 拓扑异构酶 I (topo I) 是一种松弛双链 DNA 螺旋应变的酶。 Topo I 在 DNA 复制中起着至关重要的作用。 它也是一些抑制拓扑I催化机制的抗癌药物的有吸引力的靶点。我们最近确定了拓扑I与其底物DNA和抗癌药物的三元复合物的结构。 Topo I 晶体的衍射通常非常弱。 我们要求同步加速器射束时间在额外的拓扑 I 复合晶体上收集 X 射线衍射数据，以便我们正在进行的新型拓扑 I 抑制剂的设计和开发。