STRUCTURAL STUDIES OF THE CLASS I LIGASE RIBOZYME

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。从随机序列中从头产生I类连接酶核酶。这种催化RNA加速了一个小的寡核苷酸的3‘OH对它自己的5’-末端三磷酸的攻击，产生了3‘-5’磷酸二酯键和焦磷酸。我们已经产生了核酶的变种，通过进行引物延伸来产生一种通用的聚合酶核酶，这种核酶可以延伸任何模板-引物对，通常最多延伸14个核苷酸。在RNA世界假说中，这种依赖于RNA的RNA聚合酶活性将是导致生命起源的过程的关键组成部分。因此，为了了解这种原始酶学的结构基础，I类连接酶核酶是一个非常有吸引力的结晶学分析的目标。

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 was generated de novo from random sequences. This catalytic RNA accelerates the attack of a small oligonucleotide's 3'OH on its own 5'-terminal triphosphate, yielding a 3'-5' phosphodiester linkage and pyrophosphate. We have generated variants of the ribozyme which are perform primer extension to produced a general polymerase ribozyme which can extend any template-primer pair, often by up to 14 nucleotides. In the RNA world hypothesis, this type of RNA-dependent RNA-polymerase activity would have been a critical component of the processes that led to the origins of life. Thus the class I ligase ribozyme is an extremely attractive target for crystallographic analysis in order to understand the structural basis for this primordial enzymology.