View source for 4bn4


==Structure of human SIRT3 in complex with ADP-ribose==
<StructureSection load='4bn4' size='340' side='right'caption='[[4bn4]], [[Resolution|resolution]] 1.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4bn4]] is a 1 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=4BN4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BN4 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]] 1.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AR6:[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHYL+[HYDROXY-[[(2R,3S,4R,5S)-3,4,5-TRIHYDROXYOXOLAN-2-YL]METHOXY]PHOSPHORYL]+HYDROGEN+PHOSPHATE'>AR6</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=OP2:2-[2-[2-[2-[2-(2-HYDROXYETHYLOXY)ETHOXY]ETHOXY]ETHOXY]ETHOXY]ETHANOIC+ACID'>OP2</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=4bn4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bn4 OCA], [https://pdbe.org/4bn4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bn4 RCSB], [https://www.ebi.ac.uk/pdbsum/4bn4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bn4 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SIR3_HUMAN SIR3_HUMAN] NAD-dependent protein deacetylase. Activates mitochondrial target proteins, including ACSS1, IDH2 and GDH by deacetylating key lysine residues. Contributes to the regulation of the cellular energy metabolism. Important for regulating tissue-specific ATP levels.<ref>PMID:16788062</ref> <ref>PMID:18680753</ref> <ref>PMID:18794531</ref> <ref>PMID:19535340</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Sirtuins are NAD(+)-dependent protein deacetylases that regulate metabolism and aging processes and are considered to be attractive therapeutic targets. Most available sirtuin modulators are little understood mechanistically, hindering their improvement. SRT1720 was initially described as an activator of human Sirt1, but it also potently inhibits human Sirt3. Here, the molecular mechanism of the inhibition of Sirt3 by SRT1720 is described. A crystal structure of Sirt3 in complex with SRT1720 and an NAD(+) analogue reveals that the compound partially occupies the acetyl-Lys binding site, thus explaining the reported competition with the peptide substrate. The compound packs against a hydrophobic protein patch and binds with its opposite surface to the NAD(+) nicotinamide, resulting in an exceptionally tight sandwich-like interaction. The observed arrangement rationalizes the uncompetitive inhibition with NAD(+), and binding measurements confirm that the nicotinamide moiety of NAD(+) supports inhibitor binding. Consistently, no inhibitor is bound in a second crystal structure of Sirt3 that was solved complexed with ADP-ribose and crystallized in the presence of SRT1720. These results reveal a novel sirtuin inhibitor binding site and mechanism, and provide a structural basis for compound improvement.

Structures of human sirtuin 3 complexes with ADP-ribose and with carba-NAD(+) and SRT1720: binding details and inhibition mechanism.,Nguyen GT, Schaefer S, Gertz M, Weyand M, Steegborn C Acta Crystallogr D Biol Crystallogr. 2013 Aug;69(Pt 8):1423-32. doi:, 10.1107/S0907444913015448. Epub 2013 Jul 17. PMID:23897466<ref>PMID:23897466</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4bn4" style="background-color:#fffaf0;"></div>

==See Also==
*[[Histone deacetylase 3D structures|Histone deacetylase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Gertz M]]
[[Category: Nguyen GTT]]
[[Category: Schaefer S]]
[[Category: Steegborn C]]
[[Category: Weyand M]]