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| | ==Solution structure of human protein C6orf130 in complex with ADP-ribose== | | ==Solution structure of human protein C6orf130 in complex with ADP-ribose== |
| - | <StructureSection load='2l8r' size='340' side='right'caption='[[2l8r]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2l8r' size='340' side='right'caption='[[2l8r]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2l8r]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L8R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2L8R FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2l8r]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L8R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2L8R FirstGlance]. <br> |
| - | </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></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2jyc|2jyc]], [[2lgr|2lgr]]</div></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></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">C6orf130 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2l8r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l8r OCA], [https://pdbe.org/2l8r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2l8r RCSB], [https://www.ebi.ac.uk/pdbsum/2l8r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2l8r 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=2l8r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l8r OCA], [https://pdbe.org/2l8r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2l8r RCSB], [https://www.ebi.ac.uk/pdbsum/2l8r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2l8r ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/OARD1_HUMAN OARD1_HUMAN]] Deacetylates O-acetyl-ADP ribose, a signaling molecule generated by the deacetylation of acetylated lysine residues in histones and other proteins. Catalyzes the deacylation of O-acetyl-ADP-ribose, O-propionyl-ADP-ribose and O-butyryl-ADP-ribose, yielding ADP-ribose plus acetate, propionate and butyrate, respectively.
| + | [https://www.uniprot.org/uniprot/OARD1_HUMAN OARD1_HUMAN] Deacetylates O-acetyl-ADP ribose, a signaling molecule generated by the deacetylation of acetylated lysine residues in histones and other proteins. Catalyzes the deacylation of O-acetyl-ADP-ribose, O-propionyl-ADP-ribose and O-butyryl-ADP-ribose, yielding ADP-ribose plus acetate, propionate and butyrate, respectively. |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Post-translational modification of proteins/histones by lysine acylation has profound effects on the physiological function of modified proteins. Deacylation by NAD(+)-dependent sirtuin reactions yields as a product O-acyl-ADP-ribose, which has been implicated as a signaling molecule in modulating cellular processes. Macrodomain-containing proteins are reported to bind NAD(+)-derived metabolites. Here, we describe the structure and function of an orphan macrodomain protein, human C6orf130. This unique 17-kDa protein is a stand-alone macrodomain protein that occupies a distinct branch in the phylogenic tree. We demonstrate that C6orf130 catalyzes the efficient deacylation of O-acetyl-ADP-ribose, O-propionyl-ADP-ribose, and O-butyryl-ADP-ribose to produce ADP-ribose (ADPr) and acetate, propionate, and butyrate, respectively. Using NMR spectroscopy, we solved the structure of C6orf130 in the presence and absence of ADPr. The structures showed a canonical fold with a deep ligand (ADPr)-binding cleft. Structural comparisons of apo-C6orf130 and the ADPr-C6orf130 complex revealed fluctuations of the beta(5)-alpha(4) loop that covers the bound ADPr, suggesting that the beta(5)-alpha(4) loop functions as a gate to sequester substrate and offer flexibility to accommodate alternative substrates. The ADPr-C6orf130 complex identified amino acid residues involved in substrate binding and suggested residues that function in catalysis. Site-specific mutagenesis and steady-state kinetic analyses revealed two critical catalytic residues, Ser-35 and Asp-125. We propose a catalytic mechanism for deacylation of O-acyl-ADP-ribose by C6orf130 and discuss the biological implications in the context of reversible protein acylation at lysine residues.
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| - | Orphan Macrodomain Protein (Human C6orf130) Is an O-Acyl-ADP-ribose Deacylase: SOLUTION STRUCTURE AND CATALYTIC PROPERTIES.,Peterson FC, Chen D, Lytle BL, Rossi MN, Ahel I, Denu JM, Volkman BF J Biol Chem. 2011 Oct 14;286(41):35955-65. Epub 2011 Aug 17. PMID:21849506<ref>PMID:21849506</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 2l8r" style="background-color:#fffaf0;"></div>
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| - | == References ==
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| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Lytle BL]] |
| - | [[Category: Lytle, B L]] | + | [[Category: Peterson FC]] |
| - | [[Category: Peterson, F C]] | + | [[Category: Volkman BF]] |
| - | [[Category: Volkman, B F]] | + | |
| - | [[Category: Cesg]]
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| - | [[Category: Deacylase]]
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| - | [[Category: Hydrolase]]
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| - | [[Category: Macro domain]]
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| - | [[Category: PSI, Protein structure initiative]]
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