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New page: left|200px<br /><applet load="1m2g" size="450" color="white" frame="true" align="right" spinBox="true" caption="1m2g, resolution 1.70Å" /> '''Sir2 homologue-ADP r...
 
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[[Image:1m2g.gif|left|200px]]<br /><applet load="1m2g" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1m2g, resolution 1.70&Aring;" />
'''Sir2 homologue-ADP ribose complex'''<br />


==Overview==
==Sir2 homologue-ADP ribose complex==
The NAD-dependent histone/protein deacetylase activity of Sir2 (silent, information regulator 2) accounts for its diverse biological roles, including gene silencing, DNA damage repair, cell cycle regulation, and, life span extension. We provide crystallographic evidence that 2'-O-acetyl, ADP-ribose is the reaction product that is formed at the active site of, Sir2 from the 2.6-A co-crystal structure of 2'-O-acetyl-ADP-ribose and, Sir2 from Archaeoglobus fulgidus. In addition, we show that His-116 and, Phe-159 play critical roles in the catalysis and substrate recognition., The conserved Ser-24 and Asp-101 contribute to the stability for NAD, binding rather than being directly involved in the catalysis. The crystal, structures of wild type and mutant derivatives of Sir2, in conjunction, with biochemical analyses of the mutants, provide novel insights into the, reaction mechanism of Sir2-mediated deacetylation.
<StructureSection load='1m2g' size='340' side='right'caption='[[1m2g]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
 
== Structural highlights ==
==About this Structure==
<table><tr><td colspan='2'>[[1m2g]] is a 1 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=1M2G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1M2G FirstGlance]. <br>
1M2G 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 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=1M2G OCA].  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
 
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=APR:ADENOSINE-5-DIPHOSPHORIBOSE'>APR</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
==Reference==
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1m2g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m2g OCA], [https://pdbe.org/1m2g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1m2g RCSB], [https://www.ebi.ac.uk/pdbsum/1m2g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1m2g ProSAT]</span></td></tr>
Structural basis for the NAD-dependent deacetylase mechanism of Sir2., Chang JH, Kim HC, Hwang KY, Lee JW, Jackson SP, Bell SD, Cho Y, J Biol Chem. 2002 Sep 13;277(37):34489-98. Epub 2002 Jun 28. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12091395 12091395]
</table>
== Function ==
[https://www.uniprot.org/uniprot/NPD1_ARCFU NPD1_ARCFU] NAD-dependent lysine deacetylase and desuccinylase that specifically removes acetyl and succinyl groups on target proteins. Modulates the activities of several proteins which are inactive in their acylated 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).<ref>PMID:10841563</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/m2/1m2g_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=1m2g ConSurf].
<div style="clear:both"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Archaeoglobus fulgidus]]
[[Category: Archaeoglobus fulgidus]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Chang, J.]]
[[Category: Chang J]]
[[Category: Cho, Y.]]
[[Category: Cho Y]]
[[Category: APR]]
[[Category: ZN]]
[[Category: protein-ligand complex]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 21:05:22 2007''

Latest revision as of 13:26, 13 March 2024

Sir2 homologue-ADP ribose complex

1m2g, resolution 1.70Å

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