1nuv: Difference between revisions

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

[[Image:1nuv.gif|left|200px]]<br /><applet load="1nuv" size="350" color="white" frame="true" align="right" spinBox="true"

caption="1nuv, resolution 1.81Å" />

'''The Leadzyme Ribozyme Bound to Mg(H2O)6(II) and Sr(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.

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==

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

1NUV is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=SR:'>SR</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NUV 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12911297 12911297]

[[Category: Protein complex]]

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

[[Category: Mckay, D B.]]

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

[[Category: Wedekind, J E.]]

[[Category: MG]]

[[Category: SR]]

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[[Category: sticky ends]]

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@@ Line 1: / Line 1: @@
-[[Image:1nuv.gif|left|200px]]<br /><applet load="1nuv" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1nuv.gif|left|200px]]<br /><applet load="1nuv" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1nuv, resolution 1.81&Aring;" />
 '''The Leadzyme Ribozyme Bound to Mg(H2O)6(II) and Sr(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.
+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==
-NUV is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with MG and SR as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1NUV OCA].
+NUV is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=SR:'>SR</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NUV 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12911297 12911297]
 [[Category: Protein complex]]
-[[Category: Mckay, D.B.]]
+[[Category: Mckay, D B.]]
-[[Category: Wedekind, J.E.]]
+[[Category: Wedekind, J E.]]
 [[Category: MG]]
 [[Category: SR]]
@@ Line 29: / Line 29: @@
 [[Category: sticky ends]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sat Nov 24 23:50:47 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:10:12 2008''