View source for 8g20


==Crystal Structure of Danio rerio histone deacetylase 6 catalytic domain 2 complexed with inhibitor Mz327==
<StructureSection load='8g20' size='340' side='right'caption='[[8g20]], [[Resolution|resolution]] 1.77&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8g20]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8G20 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8G20 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]] 1.766&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EOH:ETHANOL'>EOH</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=YJ5:4-[(N-butylpentanamido)methyl]-N-hydroxybenzamide'>YJ5</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=8g20 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8g20 OCA], [https://pdbe.org/8g20 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8g20 RCSB], [https://www.ebi.ac.uk/pdbsum/8g20 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8g20 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A7YT55_DANRE A7YT55_DANRE] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Dysregulation of both tubulin deacetylases sirtuin 2 (Sirt2) and the histone deacetylase 6 (HDAC6) has been associated with the pathogenesis of cancer and neurodegeneration, thus making these two enzymes promising targets for pharmaceutical intervention. Herein, we report the design, synthesis, and biological characterization of the first-in-class dual Sirt2/HDAC6 inhibitors as molecular tools for dual inhibition of tubulin deacetylation. Using biochemical in vitro assays and cell-based methods for target engagement, we identified Mz325 (33) as a potent and selective inhibitor of both target enzymes. Inhibition of both targets was further confirmed by X-ray crystal structures of Sirt2 and HDAC6 in complex with building blocks of 33. In ovarian cancer cells, 33 evoked enhanced effects on cell viability compared to single or combination treatment with the unconjugated Sirt2 and HDAC6 inhibitors. Thus, our dual Sirt2/HDAC6 inhibitors are important new tools to study the consequences and the therapeutic potential of dual inhibition of tubulin deacetylation.

Development of First-in-Class Dual Sirt2/HDAC6 Inhibitors as Molecular Tools for Dual Inhibition of Tubulin Deacetylation.,Sinatra L, Vogelmann A, Friedrich F, Tararina MA, Neuwirt E, Colcerasa A, Konig P, Toy L, Yesiloglu TZ, Hilscher S, Gaitzsch L, Papenkordt N, Zhai S, Zhang L, Romier C, Einsle O, Sippl W, Schutkowski M, Gross O, Bendas G, Christianson DW, Hansen FK, Jung M, Schiedel M J Med Chem. 2023 Nov 9;66(21):14787-14814. doi: 10.1021/acs.jmedchem.3c01385. , Epub 2023 Oct 30. PMID:37902787<ref>PMID:37902787</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8g20" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Danio rerio]]
[[Category: Large Structures]]
[[Category: Christianson DW]]
[[Category: Tararina MA]]