title: Structural basis for Diels-Alder ribozyme-catalyzed carbon-carbon bond formation.
abstract: The majority of structural efforts addressing RNA's catalytic function have focused on natural ribozymes, which catalyze phosphodiester transfer reactions. By contrast, little is known about how RNA catalyzes other types of chemical reactions. We report here 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 a reaction product. The RNA adopts a lambda-shaped nested pseudoknot architecture whose preformed hydrophobic pocket is precisely complementary in shape to the reaction product. RNA folding and product binding are dictated by extensive stacking and hydrogen bonding, whereas stereoselection is governed by the shape of the catalytic 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.
authors.affiliation: Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Serganov
authors.forename: Sonja
authors.initials: S
authors.lastname: Keiper
authors.forename: Lucy
authors.initials: L
authors.lastname: Malinina
authors.forename: Valentina
authors.initials: V
authors.lastname: Tereshko
authors.forename: Eugene
authors.initials: E
authors.lastname: Skripkin
authors.forename: Claudia
authors.initials: C
authors.lastname: Höbartner
authors.forename: Anna
authors.initials: A
authors.lastname: Polonskaia
authors.forename: Anh Tuân
authors.initials: AT
authors.lastname: Phan
authors.forename: Richard
authors.initials: R
authors.lastname: Wombacher
authors.forename: Ronald
authors.initials: R
authors.lastname: Micura
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Dauter
authors.forename: Andres
authors.initials: A
authors.lastname: Jäschke
authors.forename: Dinshaw J
authors.initials: DJ
authors.lastname: Patel
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D002244:Carbon / Q000737:chemistry; D002384:Catalysis; D020134:Catalytic Domain; D003460:Crystallization; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D016337:RNA, Catalytic / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D016337:RNA, Catalytic; D002244:Carbon
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