1nuj

[[Image:1nuj.gif|left|200px]]<br /><applet load="1nuj" size="450" color="white" frame="true" align="right" spinBox="true"

caption="1nuj, resolution 1.80&Aring;" />

'''THE LEADZYME STRUCTURE BOUND TO MG(H20)6(II) AT 1.8 A RESOLUTION'''<br />

==Overview==

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.

==About this Structure==

1NUJ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with MG as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1NUJ OCA].

 

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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12911297 12911297]

[[Category: Protein complex]]

[[Category: Mckay, D.B.]]

[[Category: Wedekind, J.E.]]