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: 7358903
• 负责人: ALEXANDER A SERGANOV
• 金额: $ 2.58万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7358903
• 关键词: STRUCTURAL; ANALYSIS; CARBON; BOND; FORMATION

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.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。大多数解决 RNA 催化功能的结构研究都集中在催化磷酸二酯转移反应的天然核酶上。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。我们已经确定了核酶的晶体结构，该核酶在未结合状态和与反应产物复合的情况下通过狄尔斯-阿尔德反应催化对映选择性碳-碳键形成。 RNA采用“¿”形嵌套假结结构，其预先形成的催化口袋与反应产物显示出精确的形状互补性。 RNA 折叠和产物结合由广泛的堆积和氢键决定，而立体选择则由预先形成的口袋的形状决定。催化显然是通过邻近效应、互补效应和电子效应的结合来实现的。我们观察到核酶和抗体催化的狄尔斯-阿尔德碳-碳键形成反应的独立进化的催化口袋结构中的结构相似性。