4uu7: Difference between revisions
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''' | ==Crystal structure of zebrafish Sirtuin 5 in complex with 3-methyl- succinylated CPS1-peptide== | ||
<StructureSection load='4uu7' size='340' side='right' caption='[[4uu7]], [[Resolution|resolution]] 3.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4uu7]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UU7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UU7 FirstGlance]. <br> | |||
</td></tr><tr><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=JO3:(2R)-2-METHYLBUTANEDIOIC+ACID'>JO3</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SUH:(2S)-2-METHYLBUTANEDIOIC+ACID'>SUH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=BEZ:BENZOIC+ACID'>BEZ</scene></td></tr> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4utn|4utn]], [[4utr|4utr]], [[4utv|4utv]], [[4utx|4utx]], [[4utz|4utz]], [[4uu8|4uu8]], [[4uua|4uua]], [[4uub|4uub]]</td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4uu7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uu7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4uu7 RCSB], [http://www.ebi.ac.uk/pdbsum/4uu7 PDBsum]</span></td></tr> | |||
<table> | |||
<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> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Gertz, M.]] | |||
[[Category: Pannek, M.]] | |||
[[Category: Steegborn, C.]] | |||
[[Category: Deacylase]] | |||
[[Category: Hydrolase]] | |||
[[Category: Mitochondrial]] | |||
[[Category: Regulatory enzyme]] | |||
[[Category: Rossmann-fold]] | |||
[[Category: Sirtuin 5]] | |||
[[Category: Zinc-binding]] | |||
Revision as of 19:17, 20 August 2014
Crystal structure of zebrafish Sirtuin 5 in complex with 3-methyl- succinylated CPS1-peptideCrystal structure of zebrafish Sirtuin 5 in complex with 3-methyl- succinylated CPS1-peptide
Structural highlights
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. References
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