View source for 8z57


==Crystal structure of human Q140L-SIRT5 in complex with succinylated Prx1 fragment and ADP ribose==
<StructureSection load='8z57' size='340' side='right'caption='[[8z57]], [[Resolution|resolution]] 1.96&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8z57]] is a 2 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=8Z57 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8Z57 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]] 1.96&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8z57 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8z57 OCA], [https://pdbe.org/8z57 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8z57 RCSB], [https://www.ebi.ac.uk/pdbsum/8z57 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8z57 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 ==
SIRT5, one of the mammalian sirtuins, specifically recognizes succinyl-lysine residues on proteins and catalyzes the desuccinylation reaction. In this study, we characterized SIRT5 mutants with hydrophobic amino acid substitutions at Q140 and N141, in addition to the catalytic residue H158, known as an active site residue, by the Michaelis-Menten analysis and X-ray crystallography. Kinetic analysis showed that the catalytic efficiency (k(cat)/K(m)) of the Q140L and N141V mutants decreased to 0.02 times and 0.0038 times that of the wild-type SIRT5, respectively, with the activity of the N141V mutant becoming comparable to that of the H158M mutant. Our findings indicate that N141 contributes significantly to the desuccinylation reaction.

SIRT5 mutants reveal the role of conserved asparagine and glutamine residues in the NAD(+)-binding pocket.,Yokoyama T, Takayama Y, Mizuguchi M, Nabeshima Y, Kusaka K FEBS Lett. 2024 Sep;598(18):2269-2280. doi: 10.1002/1873-3468.14961. Epub 2024 , Jun 20. PMID:39031546<ref>PMID:39031546</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8z57" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Takayama Y]]
[[Category: Yokoyama T]]