2od9: Difference between revisions
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New page: left|200px<br /><applet load="2od9" size="450" color="white" frame="true" align="right" spinBox="true" caption="2od9, resolution 2.05Å" /> '''Structural Basis for... |
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== | ==Structural Basis for Nicotinamide Inhibition and Base Exchange in Sir2 Enzymes== | ||
The Sir2 family of proteins consists of broadly conserved NAD(+)-dependent | <StructureSection load='2od9' size='340' side='right'caption='[[2od9]], [[Resolution|resolution]] 2.05Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2od9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OD9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OD9 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1R:5-O-[(S)-{[(S)-{[(2R,3R,4S)-3,4-DIHYDROXYPYRROLIDIN-2-YL]METHOXY}(HYDROXY)PHOSPHORYL]OXY}(HYDROXY)PHOSPHORYL]ADENOSINE'>A1R</scene>, <scene name='pdbligand=ALY:N(6)-ACETYLLYSINE'>ALY</scene>, <scene name='pdbligand=NCA:NICOTINAMIDE'>NCA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2od9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2od9 OCA], [https://pdbe.org/2od9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2od9 RCSB], [https://www.ebi.ac.uk/pdbsum/2od9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2od9 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/HST2_YEAST HST2_YEAST] NAD-dependent histone deacetylase that is involved in nuclear silencing events. Derepresses subtelomeric silencing and increases repression in nucleolar (rDNA) silencing. Its function is negatively regulated by active nuclear export.<ref>PMID:10811920</ref> <ref>PMID:11106374</ref> <ref>PMID:11226170</ref> <ref>PMID:15274642</ref> <ref>PMID:17110954</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/od/2od9_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2od9 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The Sir2 family of proteins consists of broadly conserved NAD(+)-dependent deacetylases that are implicated in diverse biological processes, including DNA regulation, metabolism, and longevity. Sir2 proteins are regulated in part by the cellular concentrations of a noncompetitive inhibitor, nicotinamide, that reacts with a Sir2 reaction intermediate via a base-exchange reaction to reform NAD(+) at the expense of deacetylation. To gain a mechanistic understanding of nicotinamide inhibition in Sir2 enzymes, we captured the structure of nicotinamide bound to a Sir2 homolog, yeast Hst2, in complex with its acetyl-lysine 16 histone H4 substrate and a reaction intermediate analog, ADP-HPD. Together with related biochemical studies and structures, we identify a nicotinamide inhibition and base-exchange site that is distinct from the so-called "C pocket" binding site for the nicotinamide group of NAD(+). These results provide insights into the Sir2 mechanism of nicotinamide inhibition and have important implications for the development of Sir2-specific effectors. | |||
Structural basis for nicotinamide inhibition and base exchange in Sir2 enzymes.,Sanders BD, Zhao K, Slama JT, Marmorstein R Mol Cell. 2007 Feb 9;25(3):463-72. PMID:17289592<ref>PMID:17289592</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2od9" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Saccharomyces cerevisiae]] | [[Category: Saccharomyces cerevisiae]] | ||
[[Category: Marmorstein R]] | |||
[[Category: Marmorstein | [[Category: Sanders BD]] | ||
[[Category: Sanders | |||
