CRYSTAL STRUCTURE OF THE CATALYTIC CORE OF AN RNA POLYMERASE RIBOZYME

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，不一定是研究者的机构。 I类连接酶核酶促进在小寡核苷酸底物和其自身的5'末端之间形成3-5'磷酸二酯键，这需要亲核试剂和亲电试剂都位于沃森-克里克对的范围内。 该化学方法  是迄今为止观察到的所有催化RNA  相当于模板指导的RNA聚合的一次周转，这是RNA世界中必不可少的活动。 事实上，连接酶的微小变体能够使用外源性核苷三磷酸催化高保真模板指导的RNA聚合，并且连接酶构成一般RNA聚合酶核酶的催化核心。 为了理解RNA催化的RNA依赖性RNA聚合的基础，我们已经着手解决连接酶的晶体结构，在它催化自连接反应之前和之后。

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. The class I ligase ribozyme promotes the formation of a 3-5' phosphodiester linkage between a small oligonucleotide substrate and its own 5' terminus, requiring both the nucleophile and electrophile to be situated within the context of a Watson-Crick pair. This chemistry  among the fastest yet observed for any catalytic RNA  is equivalent to a single turnover of template-directed RNA polymerization, an activity that would have been requisite in the RNA World. Indeed, minor variants of the ligase are capable of catalyzing high-fidelity template-directed RNA polymerization using exogenous nucleoside triphosphates, and the ligase constitutes the catalytic core for a general RNA polymerase ribozyme. To understand the basis of RNA-catalyzed RNA-dependent RNA polymerization, we have set out to solve the crystal structure of the ligase, before and after it has catalyzed the self-ligation reaction.