REPLICATION COMPLEXES OF RHDV RNA-DEPENDENT RNA POLYMERASE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。兔出血症病毒（RHDV）属于钩状病毒科，是一种正义单链RNA病毒，可引起包括人类在内的哺乳动物的严重疾病。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特性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的工作使我们能够在许多不同的构象状态下解决RHDV RdRP的结构，与不同的金属离子和不同的核苷酸络合物。对核酸底物和蛋白质辅因子的结晶和解决复合物结构的初步尝试已经导致了许多新的晶体形式的鉴定。目前正在进行生物化学研究、结晶试验和结晶学研究，以便确定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.