1q17: Difference between revisions

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[[Image:1q17.gif|left|200px]]<br /><applet load="1q17" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:1q17.gif|left|200px]]<br /><applet load="1q17" size="350" color="white" frame="true" align="right" spinBox="true"

caption="1q17, resolution 2.70Å" />

'''Structure of the yeast Hst2 protein deacetylase in ternary complex with 2'-O-acetyl ADP ribose and histone peptide'''<br />

==Overview==

Sir2 proteins are NAD(+)-dependant protein deactylases that have been, implicated in playing roles in gene silencing, DNA repair, genome, stability, longevity, metabolism, and cell physiology. To define the, mechanism of Sir2 activity, we report the 1.5 A crystal structure of the, yeast Hst2 (yHst2) Sir2 protein in ternary complex with 2'-O-acetyl ADP, ribose and an acetylated histone H4 peptide. The structure captures both, ligands meeting within an enclosed tunnel between the small and large, domains of the catalytic protein core and permits the assignment of a, detailed catalytic mechanism for the Sir2 proteins that is consistent with, solution and enzymatic studies. Comparison of the ternary complex with the, yHst2/NAD(+) complex, also reported here, and nascent yHst2 structure also, reveals that NAD(+) binding accompanies intramolecular loop rearrangement, for more stable NAD(+) and acetyl-lysine binding, and that acetyl-lysine, peptide binding induces a trimer-monomer protein transition involving, nonconserved Sir2 residues.

Sir2 proteins are NAD(+)-dependant protein deactylases that have been implicated in playing roles in gene silencing, DNA repair, genome stability, longevity, metabolism, and cell physiology. To define the mechanism of Sir2 activity, we report the 1.5 A crystal structure of the yeast Hst2 (yHst2) Sir2 protein in ternary complex with 2'-O-acetyl ADP ribose and an acetylated histone H4 peptide. The structure captures both ligands meeting within an enclosed tunnel between the small and large domains of the catalytic protein core and permits the assignment of a detailed catalytic mechanism for the Sir2 proteins that is consistent with solution and enzymatic studies. Comparison of the ternary complex with the yHst2/NAD(+) complex, also reported here, and nascent yHst2 structure also reveals that NAD(+) binding accompanies intramolecular loop rearrangement for more stable NAD(+) and acetyl-lysine binding, and that acetyl-lysine peptide binding induces a trimer-monomer protein transition involving nonconserved Sir2 residues.

==About this Structure==

1Q17 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with ZN, CL and APR as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1Q17 OCA].

1Q17 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=CL:'>CL</scene> and <scene name='pdbligand=APR:'>APR</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q17 OCA].

==Reference==

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[[Category: histone deacetylase]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Wed Nov~~ 21 00:17:~~52 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:34:47 2008''

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@@ Line 1: / Line 1: @@
-[[Image:1q17.gif|left|200px]]<br /><applet load="1q17" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1q17.gif|left|200px]]<br /><applet load="1q17" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1q17, resolution 2.70&Aring;" />
 '''Structure of the yeast Hst2 protein deacetylase in ternary complex with 2'-O-acetyl ADP ribose and histone peptide'''<br />
 ==Overview==
-Sir2 proteins are NAD(+)-dependant protein deactylases that have been, implicated in playing roles in gene silencing, DNA repair, genome, stability, longevity, metabolism, and cell physiology. To define the, mechanism of Sir2 activity, we report the 1.5 A crystal structure of the, yeast Hst2 (yHst2) Sir2 protein in ternary complex with 2'-O-acetyl ADP, ribose and an acetylated histone H4 peptide. The structure captures both, ligands meeting within an enclosed tunnel between the small and large, domains of the catalytic protein core and permits the assignment of a, detailed catalytic mechanism for the Sir2 proteins that is consistent with, solution and enzymatic studies. Comparison of the ternary complex with the, yHst2/NAD(+) complex, also reported here, and nascent yHst2 structure also, reveals that NAD(+) binding accompanies intramolecular loop rearrangement, for more stable NAD(+) and acetyl-lysine binding, and that acetyl-lysine, peptide binding induces a trimer-monomer protein transition involving, nonconserved Sir2 residues.
+Sir2 proteins are NAD(+)-dependant protein deactylases that have been implicated in playing roles in gene silencing, DNA repair, genome stability, longevity, metabolism, and cell physiology. To define the mechanism of Sir2 activity, we report the 1.5 A crystal structure of the yeast Hst2 (yHst2) Sir2 protein in ternary complex with 2'-O-acetyl ADP ribose and an acetylated histone H4 peptide. The structure captures both ligands meeting within an enclosed tunnel between the small and large domains of the catalytic protein core and permits the assignment of a detailed catalytic mechanism for the Sir2 proteins that is consistent with solution and enzymatic studies. Comparison of the ternary complex with the yHst2/NAD(+) complex, also reported here, and nascent yHst2 structure also reveals that NAD(+) binding accompanies intramolecular loop rearrangement for more stable NAD(+) and acetyl-lysine binding, and that acetyl-lysine peptide binding induces a trimer-monomer protein transition involving nonconserved Sir2 residues.
 ==About this Structure==
-Q17 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with ZN, CL and APR as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1Q17 OCA].
+Q17 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=CL:'>CL</scene> and <scene name='pdbligand=APR:'>APR</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q17 OCA].
 ==Reference==
@@ Line 21: / Line 21: @@
 [[Category: histone deacetylase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 00:17:52 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:34:47 2008''