4uub
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of zebrafish Sirtuin 5 in complex with 2R-butyl- succinylated CPS1-peptide== | |
| + | <StructureSection load='4uub' size='340' side='right'caption='[[4uub]], [[Resolution|resolution]] 2.90Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4uub]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UUB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UUB 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]] 2.9Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BEZ:BENZOIC+ACID'>BEZ</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</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=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SU8:(2R)-2-BUTYLBUTANEDIOIC+ACID'>SU8</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=4uub FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uub OCA], [https://pdbe.org/4uub PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4uub RCSB], [https://www.ebi.ac.uk/pdbsum/4uub PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4uub ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/SIR5_DANRE SIR5_DANRE] NAD-dependent lysine demalonylase and desuccinylase that specifically removes malonyl and succinyl groups on target proteins. Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo (By similarity). | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Sirtuins are NAD+ -dependent deacetylases acting as sensors in metabolic pathways and stress response. In mammals there are seven isoforms. The mitochondrial sirtuin 5 is a weak deacetylase but a very efficient demalonylase and desuccinylase; however, its substrate acyl specificity has not been systematically analyzed. Herein, we investigated a carbamoyl phosphate synthetase 1 derived peptide substrate and modified the lysine side chain systematically to determine the acyl specificity of Sirt5. From that point we designed six potent peptide-based inhibitors that interact with the NAD+ binding pocket. To characterize the interaction details causing the different substrate and inhibition properties we report several X-ray crystal structures of Sirt5 complexed with these peptides. Our results reveal the Sirt5 acyl selectivity and its molecular basis and enable the design of inhibitors for Sirt5. | ||
| - | + | Chemical Probing of the Human Sirtuin 5 Active Site Reveals Its Substrate Acyl Specificity and Peptide-Based Inhibitors.,Roessler C, Nowak T, Pannek M, Gertz M, Nguyen GT, Scharfe M, Born I, Sippl W, Steegborn C, Schutkowski M Angew Chem Int Ed Engl. 2014 Aug 11. doi: 10.1002/anie.201402679. PMID:25111069<ref>PMID:25111069</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 4uub" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Histone deacetylase 3D structures|Histone deacetylase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Danio rerio]] | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Gertz M]] | ||
| + | [[Category: Pannek M]] | ||
| + | [[Category: Steegborn C]] | ||
Current revision
Crystal structure of zebrafish Sirtuin 5 in complex with 2R-butyl- succinylated CPS1-peptide
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