2p7f

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{{STRUCTURE_2p7f| PDB=2p7f | SCENE= }}
{{STRUCTURE_2p7f| PDB=2p7f | SCENE= }}
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'''The Novel Use of a 2',5'-Phosphodiester Linkage as a Reaction Intermediate at the Active Site of a Small Ribozyme'''
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===The Novel Use of a 2',5'-Phosphodiester Linkage as a Reaction Intermediate at the Active Site of a Small Ribozyme===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_17488874}}
==About this Structure==
==About this Structure==
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==Reference==
==Reference==
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 Jul;13(7):1052-70. Epub 2007 May 8. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17488874 17488874]
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 Jul;13(7):1052-70. Epub 2007 May 8. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17488874 17488874]
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Water in the active site of an all-RNA hairpin ribozyme and effects of Gua8 base variants on the geometry of phosphoryl transfer., Salter J, Krucinska J, Alam S, Grum-Tokars V, Wedekind JE, Biochemistry. 2006 Jan 24;45(3):686-700. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16411744 16411744]
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Conformational heterogeneity at position U37 of an all-RNA hairpin ribozyme with implications for metal binding and the catalytic structure of the S-turn., Alam S, Grum-Tokars V, Krucinska J, Kundracik ML, Wedekind JE, Biochemistry. 2005 Nov 8;44(44):14396-408. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16262240 16262240]
[[Category: Krucinska, J.]]
[[Category: Krucinska, J.]]
[[Category: Torelli, A T.]]
[[Category: Torelli, A T.]]
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[[Category: Transition-state stabilization]]
[[Category: Transition-state stabilization]]
[[Category: Vanadate]]
[[Category: Vanadate]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 07:09:39 2008''

Revision as of 04:09, 29 July 2008

Image:2p7f.png

Template:STRUCTURE 2p7f

The Novel Use of a 2',5'-Phosphodiester Linkage as a Reaction Intermediate at the Active Site of a Small Ribozyme

Template:ABSTRACT PUBMED 17488874

About this Structure

Full crystallographic information is available from OCA.

Reference

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 Jul;13(7):1052-70. Epub 2007 May 8. PMID:17488874

Water in the active site of an all-RNA hairpin ribozyme and effects of Gua8 base variants on the geometry of phosphoryl transfer., Salter J, Krucinska J, Alam S, Grum-Tokars V, Wedekind JE, Biochemistry. 2006 Jan 24;45(3):686-700. PMID:16411744

Conformational heterogeneity at position U37 of an all-RNA hairpin ribozyme with implications for metal binding and the catalytic structure of the S-turn., Alam S, Grum-Tokars V, Krucinska J, Kundracik ML, Wedekind JE, Biochemistry. 2005 Nov 8;44(44):14396-408. PMID:16262240

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