4f4u: Difference between revisions

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-[[Image:4f4u.png|left|200px]]
-{{STRUCTURE_4f4u|  PDB=4f4u  |  SCENE=  }}
+==The bicyclic intermediate structure provides insights into the desuccinylation mechanism of SIRT5==
+<StructureSection load='4f4u' size='340' side='right'caption='[[4f4u]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4f4u]] is a 4 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=4F4U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4F4U 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&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4f4u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f4u OCA], [https://pdbe.org/4f4u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4f4u RCSB], [https://www.ebi.ac.uk/pdbsum/4f4u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4f4u ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/SIR5_HUMAN SIR5_HUMAN] NAD-dependent lysine demalonylase and desuccinylase that specifically removes malonyl and succinyl groups on target proteins. Activates CPS1 and contributes to the regulation of blood ammonia levels during prolonged fasting: acts by mediating desuccinylation of CPS1, thereby increasing CPS1 activity in response to elevated NAD levels during fasting. Activates SOD1 by mediating its desuccinylation, leading to reduced reactive oxygen species. Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) and a number of other proteins in vitro.<ref>PMID:18680753</ref> <ref>PMID:21908771</ref> <ref>PMID:24140062</ref> <ref>PMID:22076378</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Sirtuins are pivotal regulators in various cellular processes, including transcription, DNA repair, genome stability, and energy metabolism. Their functions have been generally attributed to NAD-dependent deacetylase activity. However, human SIRT5 (sirtuin 5), which has been reported to exhibit little deacetylase activity, was recently identified as an NAD-dependent demalonylase and desuccinylase. Biochemical studies suggested that the mechanism of SIRT5-catalyzed demalonylation and desuccinylation is similar to that of deacetylation catalyzed by other sirtuins. Previously, we solved the crystal structure of a SIRT5-succinyl-lysine peptide-NAD complex. Here, we present two more structures: a binary complex of SIRT5 with an H3K9 succinyl peptide and a binary complex of SIRT5 with a bicyclic intermediate obtained by incubating SIRT5-H3K9 thiosuccinyl peptide co-crystals with NAD. To our knowledge, this represents the first bicyclic intermediate for a sirtuin-catalyzed deacylation reaction that has been captured in a crystal structure, thus providing unique insights into the reaction mechanism. The structural information should benefit the design of specific inhibitors for SIRT5 and help in exploring the therapeutic potential of targeting sirtuins for treating human diseases.
-===The bicyclic intermediate structure provides insights into the desuccinylation mechanism of SIRT5===
+The Bicyclic Intermediate Structure Provides Insights into the Desuccinylation Mechanism of Human Sirtuin 5 (SIRT5).,Zhou Y, Zhang H, He B, Du J, Lin H, Cerione RA, Hao Q J Biol Chem. 2012 Aug 17;287(34):28307-14. Epub 2012 Jul 5. PMID:22767592<ref>PMID:22767592</ref>
-{{ABSTRACT_PUBMED_22767592}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 4f4u" style="background-color:#fffaf0;"></div>
-==About this Structure==
+==See Also==
-[[4f4u]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4F4U OCA].
+*[[Histone deacetylase 3D structures|Histone deacetylase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Hao, Q.]]
+[[Category: Large Structures]]
-[[Category: Zhou, Y.]]
+[[Category: Hao Q]]
-[[Category: Hydrolase]]
+[[Category: Zhou Y]]
-[[Category: Mitochondrial sirtuin]]
-[[Category: Nad-dependent demalonylase and desuccinylase]]
-[[Category: Rossmann fold domain]]
-[[Category: Zn-binding domain]]