CRYSTALLOGRAPHIC STUDIES ON HUMAN DNA TOPOISOMERASE I

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。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。人DNA拓扑异构酶I（topoisomerase I，topo I）是一种使双链DNA的螺旋张力松弛的酶。Topo I在DNA复制中起关键作用。它也是一些抑制topo 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异构酶Ⅰ与其底物DNA和抗癌药物的三元复合物的结构。拓扑异构酶I晶体通常表现得非常弱。我们要求同步加速器束时的X射线衍射数据收集额外的拓扑异构酶I复合晶体为我们正在进行的设计和开发的新型拓扑异构酶I抑制剂。

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.