View source for 6enx


==Zebrafish Sirt5 in complex with stalled bicyclic intermediate of inhibitory compound 10==
<StructureSection load='6enx' size='340' side='right' caption='[[6enx]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6enx]] is a 1 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=6ENX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ENX FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BJW:4-[(2~{R},3~{a}~{R},5~{R},6~{R},6~{a}~{R})-5-[[[[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl]oxy-oxidanyl-phosphoryl]oxymethyl]-2-[[(5~{S})-6-[[(2~{S})-3-(1~{H}-indol-3-yl)-1-oxidanylidene-1-(propan-2-ylamino)propan-2-yl]amino]-6-oxidanylidene-5-(phenylmethoxycarbonylamino)hexyl]amino]-6-oxidanyl-3~{a},5,6,6~{a}-tetrahydrofuro[2,3-d][1,3]oxathiol-2-yl]butanoic+acid'>BJW</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">sirt5, si:ch211-121a2.1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7955 Brachidanio rerio])</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=6enx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6enx OCA], [http://pdbe.org/6enx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6enx RCSB], [http://www.ebi.ac.uk/pdbsum/6enx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6enx ProSAT]</span></td></tr>
</table>
== 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). 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The sirtuin enzymes are important regulatory deacylases in a variety of biochemical contexts and may therefore be potential therapeutic targets through either activation or inhibition by small molecules. Here, we describe the discovery of the most potent inhibitor of sirtuin 5 (SIRT5) reported to date. We provide rationalization of the mode of binding by solving co-crystal structures of selected inhibitors in complex with both human and zebrafish SIRT5, which provide insight for future optimization of inhibitors with more "drug-like" properties. Importantly, enzyme kinetic evaluation revealed a slow, tight-binding mechanism of inhibition, which is unprecedented for sirtuins. This is important information when applying inhibitors to probe mechanisms in biology.

Mechanism-based Inhibitors of the Human Sirtuin 5 Deacylase: Structure-Activity Relationship, Biostructural, and Kinetic Insight.,Rajabi N, Auth M, Troelsen KR, Pannek M, Bhatt D, Fontenas M, Hirshey MD, Steegborn C, Madsen AS, Olsen CA Angew Chem Int Ed Engl. 2017 Oct 17. doi: 10.1002/anie.201709050. PMID:29044784<ref>PMID:29044784</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6enx" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Brachidanio rerio]]
[[Category: Pannek, M]]
[[Category: Steegborn, C]]
[[Category: Hydrolase]]
[[Category: Inhibitor]]
[[Category: Ptm]]
[[Category: Signaling protein]]
[[Category: Sirtuin]]