1yc2

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[[Image:1yc2.gif|left|200px]]<br /><applet load="1yc2" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1yc2.gif|left|200px]]
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caption="1yc2, resolution 2.4&Aring;" />
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'''Sir2Af2-NAD-ADPribose-nicotinamide'''<br />
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{{Structure
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|PDB= 1yc2 |SIZE=350|CAPTION= <scene name='initialview01'>1yc2</scene>, resolution 2.4&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=APR:ADENOSINE-5-DIPHOSPHORIBOSE'>APR</scene>, <scene name='pdbligand=NCA:NICOTINAMIDE'>NCA</scene>, <scene name='pdbligand=2PE:NONAETHYLENE+GLYCOL'>2PE</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene> and <scene name='pdbligand=PGE:TRIETHYLENE GLYCOL'>PGE</scene>
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|ACTIVITY=
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|GENE= npdA2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2234 Archaeoglobus fulgidus])
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}}
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'''Sir2Af2-NAD-ADPribose-nicotinamide'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1YC2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Archaeoglobus_fulgidus Archaeoglobus fulgidus] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=NAD:'>NAD</scene>, <scene name='pdbligand=APR:'>APR</scene>, <scene name='pdbligand=NCA:'>NCA</scene>, <scene name='pdbligand=2PE:'>2PE</scene>, <scene name='pdbligand=PG4:'>PG4</scene>, <scene name='pdbligand=EDO:'>EDO</scene> and <scene name='pdbligand=PGE:'>PGE</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YC2 OCA].
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1YC2 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Archaeoglobus_fulgidus Archaeoglobus fulgidus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YC2 OCA].
==Reference==
==Reference==
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Mechanism of sirtuin inhibition by nicotinamide: altering the NAD(+) cosubstrate specificity of a Sir2 enzyme., Avalos JL, Bever KM, Wolberger C, Mol Cell. 2005 Mar 18;17(6):855-68. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15780941 15780941]
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Mechanism of sirtuin inhibition by nicotinamide: altering the NAD(+) cosubstrate specificity of a Sir2 enzyme., Avalos JL, Bever KM, Wolberger C, Mol Cell. 2005 Mar 18;17(6):855-68. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15780941 15780941]
[[Category: Archaeoglobus fulgidus]]
[[Category: Archaeoglobus fulgidus]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: ternary complex]]
[[Category: ternary complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:03:51 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:20:56 2008''

Revision as of 13:20, 20 March 2008


PDB ID 1yc2

Drag the structure with the mouse to rotate
, resolution 2.4Å
Ligands: , , , , , , , and
Gene: npdA2 (Archaeoglobus fulgidus)
Coordinates: save as pdb, mmCIF, xml



Sir2Af2-NAD-ADPribose-nicotinamide


Overview

Sir2 enzymes form a unique class of NAD(+)-dependent deacetylases required for diverse biological processes, including transcriptional silencing, regulation of apoptosis, fat mobilization, and lifespan regulation. Sir2 activity is regulated by nicotinamide, a noncompetitive inhibitor that promotes a base-exchange reaction at the expense of deacetylation. To elucidate the mechanism of nicotinamide inhibition, we determined ternary complex structures of Sir2 enzymes containing nicotinamide. The structures show that free nicotinamide binds in a conserved pocket that participates in NAD(+) binding and catalysis. Based on our structures, we engineered a mutant that deacetylates peptides by using nicotinic acid adenine dinucleotide (NAAD) as a cosubstrate and is inhibited by nicotinic acid. The characteristics of the altered specificity enzyme establish that Sir2 enzymes contain a single site that participates in catalysis and nicotinamide regulation and provides additional insights into the Sir2 catalytic mechanism.

About this Structure

1YC2 is a Single protein structure of sequence from Archaeoglobus fulgidus. Full crystallographic information is available from OCA.

Reference

Mechanism of sirtuin inhibition by nicotinamide: altering the NAD(+) cosubstrate specificity of a Sir2 enzyme., Avalos JL, Bever KM, Wolberger C, Mol Cell. 2005 Mar 18;17(6):855-68. PMID:15780941

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