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| | <StructureSection load='2od2' size='340' side='right'caption='[[2od2]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='2od2' size='340' side='right'caption='[[2od2]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2od2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OD2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OD2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2od2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OD2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OD2 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CNA:CARBA-NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>CNA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ALY:N(6)-ACETYLLYSINE'>ALY</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ALY:N(6)-ACETYLLYSINE'>ALY</scene>, <scene name='pdbligand=CNA:CARBA-NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>CNA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1szc|1szc]], [[1szd|1szd]], [[2od7|2od7]], [[2od9|2od9]]</div></td></tr>
| + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HST2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824])</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=2od2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2od2 OCA], [https://pdbe.org/2od2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2od2 RCSB], [https://www.ebi.ac.uk/pdbsum/2od2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2od2 ProSAT]</span></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=2od2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2od2 OCA], [https://pdbe.org/2od2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2od2 RCSB], [https://www.ebi.ac.uk/pdbsum/2od2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2od2 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == 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>
| + | [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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc 18824]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Sanders, B D]] | + | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Hydrolase]] | + | [[Category: Sanders BD]] |
| - | [[Category: Rossmann fold]]
| + | |
| - | [[Category: Zn binding protein]]
| + | |
| Structural highlights
Function
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.[1] [2] [3] [4] [5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
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[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Landry J, Sutton A, Tafrov ST, Heller RC, Stebbins J, Pillus L, Sternglanz R. The silencing protein SIR2 and its homologs are NAD-dependent protein deacetylases. Proc Natl Acad Sci U S A. 2000 May 23;97(11):5807-11. PMID:10811920 doi:http://dx.doi.org/10.1073/pnas.110148297
- ↑ Tanner KG, Landry J, Sternglanz R, Denu JM. Silent information regulator 2 family of NAD- dependent histone/protein deacetylases generates a unique product, 1-O-acetyl-ADP-ribose. Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14178-82. PMID:11106374 doi:http://dx.doi.org/10.1073/pnas.250422697
- ↑ Perrod S, Cockell MM, Laroche T, Renauld H, Ducrest AL, Bonnard C, Gasser SM. A cytosolic NAD-dependent deacetylase, Hst2p, can modulate nucleolar and telomeric silencing in yeast. EMBO J. 2001 Jan 15;20(1-2):197-209. PMID:11226170 doi:http://dx.doi.org/10.1093/emboj/20.1.197
- ↑ Borra MT, Langer MR, Slama JT, Denu JM. Substrate specificity and kinetic mechanism of the Sir2 family of NAD+-dependent histone/protein deacetylases. Biochemistry. 2004 Aug 3;43(30):9877-87. PMID:15274642 doi:http://dx.doi.org/10.1021/bi049592e
- ↑ Wilson JM, Le VQ, Zimmerman C, Marmorstein R, Pillus L. Nuclear export modulates the cytoplasmic Sir2 homologue Hst2. EMBO Rep. 2006 Dec;7(12):1247-51. Epub 2006 Nov 17. PMID:17110954 doi:http://dx.doi.org/10.1038/sj.embor.7400829
- ↑ Sanders BD, Zhao K, Slama JT, Marmorstein R. Structural basis for nicotinamide inhibition and base exchange in Sir2 enzymes. Mol Cell. 2007 Feb 9;25(3):463-72. PMID:17289592 doi:10.1016/j.molcel.2006.12.022
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