STRUCTURE, MECHANISM AND CATALYSIS IN EVOLVED RIBOZYME AND RNA VIRUSES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们正在研究催化RNA(或核酶)和来自病毒的RNA的结构。我们在最后一次光束时间分配期间获得了SARS病毒RNA基因组高度保守的区域S2m RNA的新晶体结构，被认为对这种致病病毒的生命周期至关重要的S2m RNA，锤头状核酶的新结构(最初在各种植物卫星RNA病毒的背景下发现)，以及体外进化的RNA连接酶的新结构，该连接酶催化被认为对生前RNA世界中RNA自我复制的进化至关重要的反应。我们建议在下一个波束时间分配期间继续对所有三个RNA系统进行结构研究。具体地说，将解决SARS S2m RNA与多肽和小分子结合的共晶以及SARS RNA/蛋白质复合结构，将分析新的锤头状核酶结构的催化变异体和突变体，并将获得体外进化的RNA连接酶的预连接状态。

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. We are investigating the structures of catalytic RNAs (or ribozymes) and RNAs derived from viruses. We have obtained new crystal structures during the last beamtime allocation period of a highly conserved region of the SARS virus RNA genome called the s2m RNA, thought to be critical to the life-cycle of this pathogenic virus, a new structure of the hammerhead ribozyme (originally discovered in the context of various plant satellite RNA viruses), and a new structure of an in vitro evolved RNA ligase that catalyzes a reaction thought to be of critical importance for the evolution of RNA selfreplication in a prebiotic RNA world. We propose to continue structural investigations of all three RNA systems during the next beamtime allocation period. Specifically, cocrystals of the SARS s2m RNA bound to peptides and small molecules, as well as SARS RNA/protein complex structures, will be solved, catalytic variants and mutants of the new hammerhead ribozyme structure will be analyzed, and a pre-ligation state of the in vitro evolved RNA ligase will be obtained.