STRUCTURAL ANALYSIS OF CARBON-CARBON BOND FORMATION CATALYZED BY RIBOZYME

核酶催化碳-碳键形成的结构分析

• 批准号: 7957307
• 负责人: ALEXANDER A SERGANOV
• 金额: $ 0.74万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7957307
• 关键词: Address; Adopted; Alder plant; Antibodies; Architecture; Binding; Carbon; Catalysis; Catalytic RNA; Complex; Computer Retrieval of Information on Scientific Projects Database; Crystallography; Diels Alder reaction; Electronics; Funding; Grant; Hydrogen Bonding; Institution; Light; RNA; RNA Folding; Reaction; Research; Research Personnel; Resources; Shapes; Source; Structure; Synchrotrons; United States National Institutes of Health; chemical reaction; phosphodiester

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 majority of structural efforts addressing RNA¿¿¿¿¿"s catalytic function have focused on natural ribozymes, which catalyze phosphodiester transfer reactions. By contrast, very little is known on how RNA can catalyze other types of chemical reactions. We have determined the crystal structures of a ribozyme that catalyzes enantioselective carbon-carbon bond formation by the Diels-Alder reaction in the unbound state and in complex with reaction product. The RNA adopts a ¿}¿¿-shaped nested pseudoknot architecture, whose pre-formed catalytic pocket shows precise shape-complementarity to the reaction product. RNA folding and product binding are dictated by extensive stacking and hydrogen-bonding, while stereoselection is governed by the shape of the preformed pocket. Catalysis is apparently achieved by a combination of proximity, complementarity, and electronic effects. We observe structural parallels in the independently evolved catalytic pocket architectures for ribozyme- and antibody-catalyzed Diels-Alder carbon-carbon bond forming reactions.

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 研究中心，而研究中心不一定是研究者所在的机构。 大多数关于RNA催化功能的结构研究都集中在天然核酶上，它催化磷酸二酯转移反应。相比之下，人们对RNA如何催化其他类型的化学反应知之甚少。我们已经确定了一种核酶的晶体结构，该核酶在未结合状态下和与反应产物的复合物中催化Diels-Alder反应形成对映选择性的碳-碳键。RNA采用了一种}¿的嵌套假结结构，其预形成的催化口袋显示出与反应产物精确的形状互补性。RNA折叠和产物结合由广泛的堆叠和氢键决定，而立体选择由预制口袋的形状决定。催化作用显然是通过邻近性、互补性和电子效应的结合来实现的。我们观察到在独立进化的催化口袋架构的核酶和抗体催化的狄尔斯-阿尔德碳-碳键形成反应的结构平行。