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| - | [[Image:2od2.gif|left|200px]] | |
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| - | {{Structure
| + | ==Crystal Structure of yHst2 I117F mutant bound to carba-NAD+ and an acetylated H4 peptide== |
| - | |PDB= 2od2 |SIZE=350|CAPTION= <scene name='initialview01'>2od2</scene>, resolution 2.000Å
| + | <StructureSection load='2od2' size='340' side='right'caption='[[2od2]], [[Resolution|resolution]] 2.00Å' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND= <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> | + | <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> |
| - | |ACTIVITY=
| + | </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> |
| - | |GENE= HST2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae])
| + | <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> |
| - | |DOMAIN=
| + | <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> |
| - | |RELATEDENTRY=[[1szc|1SZC]], [[1szd|1SZD]], [[2od7|2OD7]], [[2od9|2OD9]]
| + | </table> |
| - | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2od2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2od2 OCA], [http://www.ebi.ac.uk/pdbsum/2od2 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2od2 RCSB]</span>
| + | == 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 == |
| - | '''Crystal Structure of yHst2 I117F mutant bound to carba-NAD+ and an acetylated H4 peptide'''
| + | [[Image:Consurf_key_small.gif|200px|right]] |
| - | | + | Check<jmol> |
| - | | + | <jmolCheckbox> |
| - | ==Overview== | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/od/2od2_consurf.spt"</scriptWhenChecked> |
| - | 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.
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| - | | + | <text>to colour the structure by Evolutionary Conservation</text> |
| - | ==About this Structure== | + | </jmolCheckbox> |
| - | 2OD2 is a [[Single protein]] structure of sequence from [http://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].
| + | </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=2od2 ConSurf]. |
| - | | + | <div style="clear:both"></div> |
| - | ==Reference== | + | == References == |
| - | 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:[http://www.ncbi.nlm.nih.gov/pubmed/17289592 17289592]
| + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Saccharomyces cerevisiae]] | | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Single protein]]
| + | [[Category: Sanders BD]] |
| - | [[Category: Sanders, B D.]] | + | |
| - | [[Category: rossmann fold]]
| + | |
| - | [[Category: zn binding protein]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:15:59 2008''
| + | |
| 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.
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
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