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| | {{STRUCTURE_1nuj| PDB=1nuj | SCENE= }} | | {{STRUCTURE_1nuj| PDB=1nuj | SCENE= }} |
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| - | '''THE LEADZYME STRUCTURE BOUND TO MG(H20)6(II) AT 1.8 A RESOLUTION'''
| + | ===THE LEADZYME STRUCTURE BOUND TO MG(H20)6(II) AT 1.8 A RESOLUTION=== |
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| - | ==Overview==
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| - | The leadzyme is a small ribozyme, derived from in vitro selection, which catalyzes site specific, Pb(2+)-dependent RNA cleavage. Pb(2+) is required for activity; Mg(2+) inhibits activity, while many divalent and trivalent ions enhance it. The leadzyme structure consists of an RNA duplex interrupted by a trinucleotide bulge. Here, crystal structures determined to 1.8 A resolution, both with Mg(2+) as the sole divalent counterion and with Mg(2+) and Sr(2+) (which mimics Pb(2+) with respect to binding but not catalysis), reveal the metal ion interactions with both the ground state and precatalytic conformations of the leadzyme. Mg(H(2)O)(6)(2+) ions bridge complementary strands of the duplex at multiple locations by binding tandem purines of one RNA strand in the major groove. At one site, Mg(H(2)O)(6)(2+) ligates the phosphodiester backbone of the trinucleotide bulge in the ground state conformation, but not in the precatalytic conformation, suggesting (a) Mg(2+) may inhibit leadzyme activity by stabilizing the ground state and (b) metal ions which displace Mg(2+) from this site may activate the leadzyme. Binding of Sr(2+) to the presumed catalytic Pb(2+) site in the precatalytic leadzyme induces local structural changes in a manner that would facilitate alignment of the catalytic ribose 2'-hydroxyl with the scissile bond for cleavage. These data support a model wherein binding of a catalytic ion to a precatalytic conformation of the leadzyme, in conjunction with the flexibility of the trinucleotide bulge, may facilitate structural rearrangements around the scissle phosphodiester bond favoring configurations that allow bond cleavage. | + | The line below this paragraph, {{ABSTRACT_PUBMED_12911297}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 12911297 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_12911297}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Rna]] | | [[Category: Rna]] |
| | [[Category: Sticky end]] | | [[Category: Sticky end]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 02:59:46 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 13:45:05 2008'' |
Revision as of 10:45, 28 July 2008
Template:STRUCTURE 1nuj
THE LEADZYME STRUCTURE BOUND TO MG(H20)6(II) AT 1.8 A RESOLUTION
Template:ABSTRACT PUBMED 12911297
About this Structure
Full crystallographic information is available from OCA.
Reference
Crystal structure of the leadzyme at 1.8 A resolution: metal ion binding and the implications for catalytic mechanism and allo site ion regulation., Wedekind JE, McKay DB, Biochemistry. 2003 Aug 19;42(32):9554-63. PMID:12911297
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