REPLICATION COMPLEXES OF RHDV RNA-DEPENDENT RNA POLYMERASE

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。兔出血症病毒(RHDV)属于杯状病毒科，是一种能引起包括人类在内的哺乳动物严重疾病的阳性单链RNA病毒家族。病毒RNA依赖的RNA聚合酶(RdRP)是复制病毒基因组所必需的。因此，了解这种酶的结构和酶学性质为开发干扰病毒复制的抗病毒治疗剂开辟了道路。以前在SSRL的工作使我们能够解决RHDV RdRP在许多不同构象状态下的结构，在与不同金属离子的络合物中，在与不同核苷酸的络合物中。对与核酸底物和蛋白质辅因子形成的络合物的结晶和结构的初步尝试导致了一些新的晶型的鉴定。目前正在进行生化研究、结晶试验和结晶学研究，以确定RHDV RdRP复制复合体的高分辨率结构。

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. Rabbit Hemorrhagic disease virus (RHDV) belongs to the Caliciviridae, a family of positive-sense, single-stranded RNA viruses causing serious diseases in mammals, including humans. The viral RNA-dependent RNA polymerase (RdRP) is essential for replicating the viral genome. Hence, understanding the structural and enzymological properties of this enzyme opens avenues for developing antiviral therapeutic agents that interfere with viral replication. Previous work at SSRL has allowed us to solve structures of RHDV RdRP in a number of different conformational states, in complex with different metal ions and in complex with different nucleotides. Preliminary attempts to crystallize and solve structures of complexes with nucleic acid substrates and protein cofactors have led to the identification of a number of new crystal forms. Ongoing biochemical studies, crystallization trials and crystallographic studies are now being carried out to allow for the determination of high-resolution structures of replication complexes of RHDV RdRP.