title: Transition state stabilization by a catalytic RNA.
abstract: The hairpin ribozyme catalyzes sequence-specific cleavage of RNA through transesterification of the scissile phosphate. Vanadate has previously been used as a transition state mimic of protein enzymes that catalyze the same reaction. Comparison of the 2.2 angstrom resolution structure of a vanadate-hairpin ribozyme complex with structures of precursor and product complexes reveals a rigid active site that makes more hydrogen bonds to the transition state than to the precursor or product. Because of the paucity of RNA functional groups capable of general acid-base or electrostatic catalysis, transition state stabilization is likely to be an important catalytic strategy for ribozymes.
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109-1024, USA.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Rupert
authors.forename: Archna P
authors.initials: AP
authors.lastname: Massey
authors.forename: Snorri Th
authors.initials: ST
authors.lastname: Sigurdsson
authors.forename: Adrian R
authors.initials: AR
authors.lastname: Ferré-D'Amaré
mesh_terms: D001665:Binding Sites; D002384:Catalysis; D003460:Crystallization; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D008024:Ligands; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism; D016337:RNA, Catalytic / Q000737:chemistry* / Q000378:metabolism*; D014638:Vanadates / Q000737:chemistry / Q000378:metabolism
chemical_list: D008024:Ligands; D016337:RNA, Catalytic; D014638:Vanadates; D010100:Oxygen