2p7e
Vanadate at the Active Site of a Small Ribozyme Suggests a Role for Water in Transition-State Stabilization
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OverviewOverview
The potential for water to participate in RNA catalyzed reactions has been, the topic of several recent studies. Here, we report crystals of a, minimal, hinged hairpin ribozyme in complex with the transition-state, analog vanadate at 2.05 A resolution. Waters are present in the active, site and are discussed in light of existing views of catalytic strategies, employed by the hairpin ribozyme. A second structure harboring a, 2',5'-phosphodiester linkage at the site of cleavage was also solved at, 2.35 A resolution and corroborates the assignment of active site waters in, the structure containing vanadate. A comparison of the two structures, reveals that the 2',5' structure adopts a conformation that resembles the, reaction intermediate in terms of (1) the positioning of its nonbridging, oxygens and (2) the covalent attachment of the 2'-O nucleophile with the, scissile G+1 phosphorus. The 2',5'-linked structure was then overlaid with, scissile bonds of other small ribozymes including the glmS, metabolite-sensing riboswitch and the hammerhead ribozyme, and suggests, the potential of the 2',5' linkage to elicit a reaction-intermediate, conformation without the need to form metalloenzyme complexes. The hairpin, ribozyme structures presented here also suggest how water molecules bound, at each of the nonbridging oxygens of G+1 may electrostatically stabilize, the transition state in a manner that supplements nucleobase functional, groups. Such coordination has not been reported for small ribozymes, but, is consistent with the structures of protein enzymes. Overall, this work, establishes significant parallels between the RNA and protein enzyme, worlds.
About this StructureAbout this Structure
2P7E is a Protein complex structure of sequences from [1] with and as ligands. Full crystallographic information is available from OCA.
ReferenceReference
A comparison of vanadate to a 2'-5' linkage at the active site of a small ribozyme suggests a role for water in transition-state stabilization., Torelli AT, Krucinska J, Wedekind JE, RNA. 2007 May 8;. PMID:17488874
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