CRYSTALLOGRAPHIC STUDIES ON HUMAN DNA TOPOISOMERASE I

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。人DNA拓扑异构酶I(Topo I)是一种松弛双链DNA中螺旋张力的酶。Topo I在DNA复制中起着关键作用。它也是一些抑制Topo I催化机制的抗癌药物的一个有吸引力的靶点。我们最近确定了Topo I与其底物DNA和抗癌药物的三元配合物的结构。TOPO I晶体的衍射率一般很弱。我们要求同步加速器光束时间用于收集额外的TOPO I络合物晶体的X射线衍射数据，以用于我们正在进行的新型TOPO I抑制剂的设计和开发。

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.