1yc2

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(New page: 200px<br /><applet load="1yc2" size="450" color="white" frame="true" align="right" spinBox="true" caption="1yc2, resolution 2.4&Aring;" /> '''Sir2Af2-NAD-ADPribose...)
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[[Image:1yc2.gif|left|200px]]<br /><applet load="1yc2" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1yc2, resolution 2.4&Aring;" />
 
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'''Sir2Af2-NAD-ADPribose-nicotinamide'''<br />
 
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==Overview==
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==Sir2Af2-NAD-ADPribose-nicotinamide==
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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.
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<StructureSection load='1yc2' size='340' side='right'caption='[[1yc2]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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== Structural highlights ==
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==About this Structure==
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<table><tr><td colspan='2'>[[1yc2]] is a 5 chain structure with sequence from [https://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]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YC2 FirstGlance]. <br>
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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 ZN, SO4, NAD, APR, NCA, 2PE, PG4, EDO and PGE as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1YC2 OCA].
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2PE:NONAETHYLENE+GLYCOL'>2PE</scene>, <scene name='pdbligand=APR:ADENOSINE-5-DIPHOSPHORIBOSE'>APR</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=NCA:NICOTINAMIDE'>NCA</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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==Reference==
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1yc2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yc2 OCA], [https://pdbe.org/1yc2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1yc2 RCSB], [https://www.ebi.ac.uk/pdbsum/1yc2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1yc2 ProSAT]</span></td></tr>
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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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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/NPD2_ARCFU NPD2_ARCFU] NAD-dependent protein deacetylase which modulates the activities of several enzymes which are inactive in their acetylated form. Deacetylates the N-terminal lysine residue of Alba, the major archaeal chromatin protein and that, in turn, increases Alba's DNA binding affinity, thereby repressing transcription (By similarity).[HAMAP-Rule:MF_01121]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/yc/1yc2_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1yc2 ConSurf].
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<div style="clear:both"></div>
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__TOC__
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</StructureSection>
[[Category: Archaeoglobus fulgidus]]
[[Category: Archaeoglobus fulgidus]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Avalos, J.L.]]
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[[Category: Avalos JL]]
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[[Category: Bever, M.K.]]
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[[Category: Bever MK]]
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[[Category: Wolberger, C.]]
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[[Category: Wolberger C]]
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[[Category: 2PE]]
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[[Category: APR]]
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[[Category: EDO]]
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[[Category: NAD]]
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[[Category: NCA]]
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[[Category: PG4]]
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[[Category: PGE]]
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[[Category: SO4]]
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[[Category: ZN]]
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[[Category: adpribose]]
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[[Category: nad]]
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[[Category: nicotinamide]]
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[[Category: sir2]]
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[[Category: sirtuin]]
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[[Category: ternary complex]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 06:40:28 2007''
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Current revision

Sir2Af2-NAD-ADPribose-nicotinamide

PDB ID 1yc2

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