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: 7370472
• 负责人: LANCE J STEWART
• 金额: $ 0.19万
• 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/7370472
• 关键词: CRYSTALLOGRAPHIC; STUDIES; HUMAN; DNA; TOPOISOMERASE

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NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。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。列出的机构适用于该中心，这不一定是调查员的机构。人DNA拓扑异构酶I（Topo I）是一种酶，可在双链DNA中放松螺旋菌株。 TOPO I在DNA复制中具有关键作用。它也是某些抗癌药物的有吸引力的靶标，这些抗癌药物抑制了Topo I的催化机制。我们最近确定了Topo I与其底物DNA和抗癌药物的三元复合物的结构。 Topo I晶体通常非常微弱。我们要求对X射线衍射数据收集的X射线衍射数据收集的同步器Beamtime，用于我们的新型Topo I抑制剂的持续设计和开发。