STRUCTURE OF THE POLIOVIRUS RNA DEPENDENT RNA POLYMERASE

脊髓灰质炎病毒RNA依赖性RNA聚合酶的结构

• 批准号: 2074926
• 负责人: STEVE C SCHULTZ
• 金额: $ 23.54万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-01 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2074926
• 关键词: DNA directed RNA polymerase; X ray crystallography; binding proteins; enzyme activity; enzyme structure; poliovirus; site directed mutagenesis

DESCRIPTION: The RNA-dependent RNA polymerase of poliovirus has been investigated extensively as one of the few RNA-dependent RNA polymerases that is amenable to biochemical analyses. Dr. Schultz has solved the three-dimensional structure of the poliovirus polymerase at 2.5 Angstrom resolution by x-ray crystallography. Structural analyses will continue with refinement, analysis of other crystal forms, and co-crystallization of the polymerase with primed-template RNAs and NTPs. The structure of the poliovirus polymerase represents the fourth and final class of templete-dependent polymerases; at least one structure for each of the other three classes (DNA-dependent DNA, DNA-dependent RNA, and RNA-dependent DNA) has previously been determined. Structural comparisons of these four classes of polymerases demonstrate that whereas a majority of their structures are quite different, their palm subdomains are closely related. Conserved structural elements in the palm subdomain correspond nicely to the conserved amino acid sequence motifs derived from extensive efforts to align polymerase sequences. Once the structure of the poliovirus polymerase is sufficiently refined, a detailed and thorough analysis of the conserved polymerase sequence/structure motifs will be pursued. Preliminary analyses suggest that several modifications in the current alignments will serve for analyzing the roles of conserved amino acids and as a tool for evaluating polymerases of unknown structure. As one of very few structures of viral replication proteins, the poliovirus polymerase structure has many important implications with regard to viral replication, once the refinement of the poliovirus polymerase structure is completed. The wealth of information available from biochemical and mutational analyses will be carefully evaluated. In addition, Dr. Schultz will explore the intriguing and tremendously important possibility that oligomerization of the poliovirus polymerase is critical for its function and that extensive polymerase-polymerase interactions observed in the crystals might provide structural models for this oligomerization.

描述：脊髓灰质炎病毒的RNA依赖性RNA聚合酶已被 作为为数不多的依赖RNA的RNA聚合酶之一， 可以进行生化分析 舒尔茨博士已经解决了 脊髓灰质炎病毒聚合酶在2.5埃处的三维结构 通过X射线晶体学的分辨率。 结构分析将继续进行， 其他晶体形式的分析，以及这些晶体的共结晶。 聚合酶与引物模板RNA和NTPs。 的结构 脊髓灰质炎病毒聚合酶代表第四类也是最后一类 模板依赖性聚合酶;至少一个结构对应于另一个 三种类型（DNA依赖性DNA、DNA依赖性RNA和RNA依赖性DNA） 此前已确定。 这四种结构的比较 聚合酶的种类表明，尽管它们的大多数 结构有很大的不同，它们的棕榈子域密切相关。 棕榈子域中的保守结构元素很好地对应于 保守的氨基酸序列基序来源于广泛的比对努力， 聚合酶序列。 一旦脊髓灰质炎病毒聚合酶的结构 充分完善，详细和彻底的分析保守的 聚合酶序列/结构基序。 初步分析表明，目前的一些修改 比对将用于分析保守氨基酸的作用， 作为评价未知结构的聚合酶的工具。 作为一个非常 一些病毒复制蛋白的结构，脊髓灰质炎病毒聚合酶 结构对于病毒复制具有许多重要意义， 一旦脊髓灰质炎病毒聚合酶结构的精制完成。 从生化和突变分析中获得的丰富信息 将被仔细评估。 此外，舒尔茨博士将探索 有趣的和非常重要的可能性， 脊髓灰质炎病毒聚合酶对于其功能和广泛 在晶体中观察到的聚合酶-聚合酶相互作用可能提供了 这种低聚反应的结构模型。