1s7g

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(New page: 200px<br /><applet load="1s7g" size="450" color="white" frame="true" align="right" spinBox="true" caption="1s7g, resolution 2.30&Aring;" /> '''Structural Basis for...)
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[[Image:1s7g.gif|left|200px]]<br /><applet load="1s7g" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1s7g, resolution 2.30&Aring;" />
 
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'''Structural Basis for the Mechanism and Regulation of Sir2 Enzymes'''<br />
 
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==Overview==
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==Structural Basis for the Mechanism and Regulation of Sir2 Enzymes==
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Sir2 proteins form a family of NAD(+)-dependent protein deacetylases, required for diverse biological processes, including transcriptional, silencing, suppression of rDNA recombination, control of p53 activity, regulation of acetyl-CoA synthetase, and aging. Although structures of, Sir2 enzymes in the presence and absence of peptide substrate or NAD(+), have been determined, the role of the enzyme in the mechanism of, deacetylation and NAD(+) cleavage is still unclear. Here, we present, additional structures of Sir2Af2 in several differently complexed states:, in a productive complex with NAD(+), in a nonproductive NAD(+) complex, with bound ADP-ribose, and in the unliganded state. We observe a new mode, of NAD(+) binding that seems to depend on acetyl-lysine binding, in which, the nicotinamide ring of NAD(+) is buried in the highly conserved "C", pocket of the enzyme. We propose a detailed structure-based mechanism for, deacetylation and nicotinamide inhibition of Sir2 consistent with, mutagenesis and enzymatic studies.
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<StructureSection load='1s7g' size='340' side='right'caption='[[1s7g]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1s7g]] 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=1S7G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1S7G FirstGlance]. <br>
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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]] 2.3&#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=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <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=P6G:HEXAETHYLENE+GLYCOL'>P6G</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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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=1s7g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s7g OCA], [https://pdbe.org/1s7g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1s7g RCSB], [https://www.ebi.ac.uk/pdbsum/1s7g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1s7g ProSAT]</span></td></tr>
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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/s7/1s7g_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=1s7g ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Sir2 proteins form a family of NAD(+)-dependent protein deacetylases required for diverse biological processes, including transcriptional silencing, suppression of rDNA recombination, control of p53 activity, regulation of acetyl-CoA synthetase, and aging. Although structures of Sir2 enzymes in the presence and absence of peptide substrate or NAD(+) have been determined, the role of the enzyme in the mechanism of deacetylation and NAD(+) cleavage is still unclear. Here, we present additional structures of Sir2Af2 in several differently complexed states: in a productive complex with NAD(+), in a nonproductive NAD(+) complex with bound ADP-ribose, and in the unliganded state. We observe a new mode of NAD(+) binding that seems to depend on acetyl-lysine binding, in which the nicotinamide ring of NAD(+) is buried in the highly conserved "C" pocket of the enzyme. We propose a detailed structure-based mechanism for deacetylation and nicotinamide inhibition of Sir2 consistent with mutagenesis and enzymatic studies.
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==About this Structure==
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Structural basis for the mechanism and regulation of Sir2 enzymes.,Avalos JL, Boeke JD, Wolberger C Mol Cell. 2004 Mar 12;13(5):639-48. PMID:15023335<ref>PMID:15023335</ref>
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1S7G 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, 2PE, P6G, PG4, 1PE and EDO as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1S7G OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Structural basis for the mechanism and regulation of Sir2 enzymes., Avalos JL, Boeke JD, Wolberger C, Mol Cell. 2004 Mar 12;13(5):639-48. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15023335 15023335]
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</div>
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<div class="pdbe-citations 1s7g" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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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: Boeke, J.D.]]
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[[Category: Boeke JD]]
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[[Category: Wolberger, C.]]
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[[Category: Wolberger C]]
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[[Category: 1PE]]
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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: P6G]]
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[[Category: PG4]]
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[[Category: SO4]]
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[[Category: ZN]]
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[[Category: adp-ribose]]
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[[Category: enzyme]]
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[[Category: nad+]]
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[[Category: sir2]]
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[[Category: sirtuin]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 02:10:20 2007''
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Current revision

Structural Basis for the Mechanism and Regulation of Sir2 Enzymes

PDB ID 1s7g

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