INVESTIGATION INTO THE STRUCTURAL MECHANISM OF ALLOSTERIC MODULATION OF DNA CLEA

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 我们正在研究与其靶DNA结合的内切核酸酶SgrAI的结构。 核酸内切酶是参与DNA代谢的所有方面（包括复制、重组和修复）的重要酶。 SgrAI用于保护其宿主免受侵入的噬菌体DNA，并在DNA上寡聚化，引起活化的SgrAI酶的螯合。 由寡聚化引起的活化的SgrAI切割一级位点DNA序列比未活化形式快200倍，并且在二级位点DNA序列处也更有效地切割。 次级位点在宿主DNA中不受保护，并且SgrAI的切割将导致宿主的基因组损伤，导致对激活的SgrAI酶的螯合的强选择性压力。 低聚界面，和结构的活化和未活化形式的SgrAI，研究其三维结构。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We are investigating the structure of an endonuclease, SgrAI, bound to its target DNA. Endonucleases are important enzymes involved in all aspects of DNA metabolism including replication, recombination, and repair. SgrAI serves to protect its host from invading phage DNA, and oligomerizes on DNA causing sequestration of the activated SgrAI enzyme. Activated SgrAI, caused by oligomerization, cleaves primary site DNA sequences 200 fold faster than the unactived form, and also cleaves more efficiently at secondary site DNA sequences. The secondary sites are not protected in the host DNA, and cleavage by SgrAI would result in genome damage to the host, resulting in strong selective pressure to sequestration of activated SgrAI enzymes. The oligomerization interfaces, and the structures of both activated and unactivated forms of SgrAI, are investigated for their three dimensional structures.