STRUCTURAL ANALYSIS OF CARBON-CARBON BOND FORMATION CATALYZED BY RIBOZYME

这个子项目是众多研究子项目之一

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.