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==Crystal structure of zebrafish Sirtuin 5 in complex with adipoylated CPS1-peptide== | ==Crystal structure of zebrafish Sirtuin 5 in complex with adipoylated CPS1-peptide== | ||
<StructureSection load='4utz' size='340' side='right' caption='[[4utz]], [[Resolution|resolution]] 3.30Å' scene=''> | <StructureSection load='4utz' size='340' side='right'caption='[[4utz]], [[Resolution|resolution]] 3.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4utz]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UTZ OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[4utz]] 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=4UTZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UTZ FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0L1:HEXANEDIOIC+ACID'>0L1</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=ZN:ZINC+ION'>ZN</scene> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.3Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0L1:HEXANEDIOIC+ACID'>0L1</scene>, <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=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=4utz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4utz OCA], [https://pdbe.org/4utz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4utz RCSB], [https://www.ebi.ac.uk/pdbsum/4utz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4utz ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == 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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 18: | Line 18: | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4utz" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Histone deacetylase 3D structures|Histone deacetylase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Danio rerio]] | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Gertz M]] | ||
[[Category: | [[Category: Pannek M]] | ||
[[Category: | [[Category: Steegborn C]] | ||
Latest revision as of 14:49, 1 February 2024
Crystal structure of zebrafish Sirtuin 5 in complex with adipoylated CPS1-peptideCrystal structure of zebrafish Sirtuin 5 in complex with adipoylated CPS1-peptide
Structural highlights
FunctionSIR5_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). Publication Abstract from PubMedSirtuins 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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