title: Adenine, a hairpin ribozyme cofactor--high-pressure and competition studies.
abstract: The RNA world hypothesis assumes that life arose from ancestral RNA molecules, which stored genetic information and catalyzed chemical reactions. Although RNA catalysis was believed to be restricted to phosphate chemistry, it is now established that the RNA has much wider catalytic capacities. In this respect, we devised, in a previous study, two hairpin ribozymes (adenine-dependent hairpin ribozyme 1 and adenine-dependent hairpin ribozyme 2) that require adenine as cofactor for their reversible self-cleavage. We have now used high hydrostatic pressure to investigate the role of adenine in the catalytic activity of adenine-dependent hairpin ribozyme 1. High-pressure studies are of interest because they make it possible to determine the volume changes associated with the reactions, which in turn reflect the conformational modifications and changes in hydration involved in the catalytic mechanism. They are also relevant in the context of piezophilic organisms, as well as in relation to the extreme conditions that prevailed at the origin of life. Our results indicate that the catalytic process involves a transition state whose formation is accompanied by a positive activation volume and release of water molecules. In addition, competition experiments with adenine analogs strongly suggest that exogenous adenine replaces the adenine present at the catalytic site of the wild-type hairpin ribozyme.
authors.affiliation: Acides Nucléiques et Biophotonique, FRE 3207 CNRS, Fonctions et Interactions des Acides Nucléiques, UPMC Université Paris 06, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Ztouti
authors.forename: Hussein
authors.initials: H
authors.lastname: Kaddour
authors.forename: Francisco
authors.initials: F
authors.lastname: Miralles
authors.forename: Christophe
authors.initials: C
authors.lastname: Simian
authors.forename: Jacques
authors.initials: J
authors.lastname: Vergne
authors.forename: Guy
authors.initials: G
authors.lastname: Hervé
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Maurel
mesh_terms: D000225:Adenine / Q000737:chemistry* / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D002384:Catalysis; D006874:Hydrostatic Pressure; D007700:Kinetics; D008274:Magnesium / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D016337:RNA, Catalytic / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D016337:RNA, Catalytic; C418481:hairpin ribozyme; D008274:Magnesium; D000225:Adenine