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2h59

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(New page: 200px<br /> <applet load="2h59" size="450" color="white" frame="true" align="right" spinBox="true" caption="2h59, resolution 1.90&Aring;" /> '''Sir2 H116A-deacetyl...)
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[[Image:2h59.gif|left|200px]]<br />
 
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<applet load="2h59" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2h59, resolution 1.90&Aring;" />
 
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'''Sir2 H116A-deacetylated p53 peptide-3'-o-acetyl ADP ribose'''<br />
 
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==Overview==
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==Sir2 H116A-deacetylated p53 peptide-3'-o-acetyl ADP ribose==
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Sirtuin proteins comprise a unique class of NAD+-dependent protein, deacetylases. Although several structures of sirtuins have been, determined, the mechanism by which NAD+ cleavage occurs has remained, unclear. We report the structures of ternary complexes containing NAD+ and, acetylated peptide bound to the bacterial sirtuin Sir2Tm and to a, catalytic mutant (Sir2Tm(H116Y)). NAD+ in these structures binds in a, conformation different from that seen in previous structures, exposing the, alpha face of the nicotinamide ribose to the carbonyl oxygen of the acetyl, lysine substrate. The NAD+ conformation is identical in both structures, suggesting that proper coenzyme orientation is not dependent on contacts, with the catalytic histidine. We also present the structure of, Sir2Tm(H116A) bound to deacteylated peptide and 3'-O-acetyl ADP ribose., Taken together, these structures suggest a mechanism for nicotinamide, cleavage in which an invariant phenylalanine plays a central role in, promoting formation of the O-alkylamidate reaction intermediate and, preventing nicotinamide exchange.
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<StructureSection load='2h59' size='340' side='right'caption='[[2h59]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2h59]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Thermotoga_maritima Thermotoga maritima]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H59 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2H59 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]] 1.9&#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=3OD:(2S,3S,4R,5S)-2-({[(S)-{[(S)-{[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methoxy}(hydroxy)phosphoryl]oxy}(hydroxy)phosphoryl]oxy}methyl)-4,5-dihydroxytetrahydrofuran-3-yl+acetate+(non-preferred+name)'>3OD</scene>, <scene name='pdbligand=APR:ADENOSINE-5-DIPHOSPHORIBOSE'>APR</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=2h59 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h59 OCA], [https://pdbe.org/2h59 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2h59 RCSB], [https://www.ebi.ac.uk/pdbsum/2h59 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2h59 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/NPD_THEMA NPD_THEMA] NAD-dependent protein deacetylase which modulates the activities of several enzymes which are inactive in their acetylated form. Has also depropionylation activity in vitro. Also able to ADP-ribosylate peptide substrates with Arg or Lys in the +2 position. The role of this function in vivo is not clear.<ref>PMID:17684016</ref> <ref>PMID:16905097</ref> <ref>PMID:19801667</ref>
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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/h5/2h59_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2h59 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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Sirtuin proteins comprise a unique class of NAD+-dependent protein deacetylases. Although several structures of sirtuins have been determined, the mechanism by which NAD+ cleavage occurs has remained unclear. We report the structures of ternary complexes containing NAD+ and acetylated peptide bound to the bacterial sirtuin Sir2Tm and to a catalytic mutant (Sir2Tm(H116Y)). NAD+ in these structures binds in a conformation different from that seen in previous structures, exposing the alpha face of the nicotinamide ribose to the carbonyl oxygen of the acetyl lysine substrate. The NAD+ conformation is identical in both structures, suggesting that proper coenzyme orientation is not dependent on contacts with the catalytic histidine. We also present the structure of Sir2Tm(H116A) bound to deacteylated peptide and 3'-O-acetyl ADP ribose. Taken together, these structures suggest a mechanism for nicotinamide cleavage in which an invariant phenylalanine plays a central role in promoting formation of the O-alkylamidate reaction intermediate and preventing nicotinamide exchange.
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==Disease==
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Insights into the sirtuin mechanism from ternary complexes containing NAD+ and acetylated peptide.,Hoff KG, Avalos JL, Sens K, Wolberger C Structure. 2006 Aug;14(8):1231-40. PMID:16905097<ref>PMID:16905097</ref>
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Known diseases associated with this structure: Adrenal cortical carcinoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Breast cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Colorectal cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Hepatocellular carcinoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Histiocytoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Li-Fraumeni syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Multiple malignancy syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Nasopharyngeal carcinoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Osteosarcoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Pancreatic cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Thyroid carcinoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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2H59 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Thermotoga_maritima Thermotoga maritima] with ZN, APR and 3OD as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2H59 OCA].
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</div>
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<div class="pdbe-citations 2h59" style="background-color:#fffaf0;"></div>
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==Reference==
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== References ==
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Insights into the sirtuin mechanism from ternary complexes containing NAD+ and acetylated peptide., Hoff KG, Avalos JL, Sens K, Wolberger C, Structure. 2006 Aug;14(8):1231-40. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16905097 16905097]
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<references/>
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[[Category: Protein complex]]
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
[[Category: Thermotoga maritima]]
[[Category: Thermotoga maritima]]
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[[Category: Avalos, J.L.]]
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[[Category: Avalos JL]]
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[[Category: Hoff, K.G.]]
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[[Category: Hoff KG]]
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[[Category: Sens, K.]]
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[[Category: Sens K]]
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[[Category: Wolberger, C.]]
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[[Category: Wolberger C]]
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[[Category: 3OD]]
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[[Category: APR]]
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[[Category: ZN]]
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[[Category: rossmann fold]]
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[[Category: zn binding domain]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 22:26:53 2007''
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Current revision

Sir2 H116A-deacetylated p53 peptide-3'-o-acetyl ADP ribose

PDB ID 2h59

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