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| | <StructureSection load='4utn' size='340' side='right'caption='[[4utn]], [[Resolution|resolution]] 3.00Å' scene=''> | | <StructureSection load='4utn' size='340' side='right'caption='[[4utn]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4utn]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Brachidanio_rerio Brachidanio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UTN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UTN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4utn]] 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=4UTN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UTN FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=BEZ:BENZOIC+ACID'>BEZ</scene>, <scene name='pdbligand=SLL:(2S)-2-AZANYL-6-[(4-HYDROXY-4-OXO-BUTANOYL)AMINO]HEXANOIC+ACID'>SLL</scene></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=SLL:(2S)-2-AZANYL-6-[(4-HYDROXY-4-OXO-BUTANOYL)AMINO]HEXANOIC+ACID'>SLL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4utr|4utr]], [[4utv|4utv]], [[4utx|4utx]], [[4utz|4utz]], [[4uu7|4uu7]], [[4uu8|4uu8]], [[4uua|4uua]], [[4uub|4uub]]</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=4utn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4utn OCA], [https://pdbe.org/4utn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4utn RCSB], [https://www.ebi.ac.uk/pdbsum/4utn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4utn ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4utn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4utn OCA], [http://pdbe.org/4utn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4utn RCSB], [http://www.ebi.ac.uk/pdbsum/4utn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4utn ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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). | + | [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 == |
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Histone deacetylase|Histone deacetylase]] | + | *[[Histone deacetylase 3D structures|Histone deacetylase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Brachidanio rerio]] | + | [[Category: Danio rerio]] |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Gertz, M]] | + | [[Category: Gertz M]] |
| - | [[Category: Pannek, M]] | + | [[Category: Pannek M]] |
| - | [[Category: Steegborn, C]] | + | [[Category: Steegborn C]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Regulatory enzyme]]
| + | |
| - | [[Category: Rossmann-fold]]
| + | |
| - | [[Category: Zinc-binding]]
| + | |
| Structural highlights
4utn is a 3 chain structure with sequence from Danio rerio and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 3Å |
| Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
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).
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Roessler C, Nowak T, Pannek M, Gertz M, Nguyen GT, Scharfe M, Born I, Sippl W, Steegborn C, Schutkowski M. Chemical Probing of the Human Sirtuin 5 Active Site Reveals Its Substrate Acyl Specificity and Peptide-Based Inhibitors. Angew Chem Int Ed Engl. 2014 Aug 11. doi: 10.1002/anie.201402679. PMID:25111069 doi:http://dx.doi.org/10.1002/anie.201402679
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