5dy5
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of human Sirt2 in complex with a SirReal probe fragment== | |
| + | <StructureSection load='5dy5' size='340' side='right'caption='[[5dy5]], [[Resolution|resolution]] 1.95Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5dy5]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DY5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DY5 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]] 1.95Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5GR:N-(5-{3-[(1-BENZYL-1H-1,2,3-TRIAZOL-4-YL)METHOXY]BENZYL}-1,3-THIAZOL-2-YL)-2-[(4,6-DIMETHYLPYRIMIDIN-2-YL)SULFANYL]ACETAMIDE'>5GR</scene>, <scene name='pdbligand=BU3:(R,R)-2,3-BUTANEDIOL'>BU3</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</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=5dy5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dy5 OCA], [https://pdbe.org/5dy5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dy5 RCSB], [https://www.ebi.ac.uk/pdbsum/5dy5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dy5 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/SIR2_HUMAN SIR2_HUMAN] NAD-dependent protein deacetylase, which deacetylates internal lysines on histone and non-histone proteins. Deacetylates 'Lys-40' of alpha-tubulin. Involved in the control of mitotic exit in the cell cycle, probably via its role in the regulation of cytoskeleton. Deacetylates PCK1, opposing proteasomal degradation. Deacetylates 'Lys-310' of RELA.<ref>PMID:12620231</ref> <ref>PMID:12697818</ref> <ref>PMID:21081649</ref> <ref>PMID:21726808</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Sirtuins are NAD+ -dependent protein deacylases that cleave off acetyl groups, as well as other acyl groups, from the epsilon-amino group of lysines in histones and other substrate proteins. Dysregulation of human Sirt2 activity has been associated with the pathogenesis of cancer, inflammation, and neurodegeneration, thus making Sirt2 a promising target for pharmaceutical intervention. Here, based on a crystal structure of Sirt2 in complex with an optimized sirtuin rearranging ligand (SirReal) that shows improved potency, water solubility, and cellular efficacy, we present the development of the first Sirt2-selective affinity probe. A slow dissociation of the probe/enzyme complex offers new applications for SirReals, such as biophysical characterization, fragment-based screening, and affinity pull-down assays. This possibility makes the SirReal probe an important tool for studying sirtuin biology. | ||
| - | + | Structure-Based Development of an Affinity Probe for Sirtuin 2.,Schiedel M, Rumpf T, Karaman B, Lehotzky A, Gerhardt S, Ovadi J, Sippl W, Einsle O, Jung M Angew Chem Int Ed Engl. 2016 Jan 8. doi: 10.1002/anie.201509843. PMID:26748890<ref>PMID:26748890</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 5dy5" style="background-color:#fffaf0;"></div> |
| - | [[Category: Gerhardt | + | |
| - | [[Category: Jung | + | ==See Also== |
| - | [[Category: | + | *[[Histone deacetylase 3D structures|Histone deacetylase 3D structures]] |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Einsle O]] | ||
| + | [[Category: Gerhardt S]] | ||
| + | [[Category: Jung M]] | ||
| + | [[Category: Rumpf T]] | ||
Current revision
Crystal structure of human Sirt2 in complex with a SirReal probe fragment
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