View source for 5kh7


==Crystal structure of fragment (3-[6-Oxo-3-(3-pyridinyl)-1(6H)-pyridazinyl]propanoic acid) bound in the ubiquitin binding pocket of the HDAC6 zinc-finger domain==
<StructureSection load='5kh7' size='340' side='right' caption='[[5kh7]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5kh7]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KH7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KH7 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6T7:3-(6-OXIDANYLIDENE-3-PYRIDIN-3-YL-PYRIDAZIN-1-YL)PROPANOIC+ACID'>6T7</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5kh3|5kh3]], [[5kh9|5kh9]], [[5b8d|5b8d]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HDAC6, KIAA0901, JM21 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone_deacetylase Histone deacetylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.98 3.5.1.98] </span></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=5kh7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kh7 OCA], [http://pdbe.org/5kh7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kh7 RCSB], [http://www.ebi.ac.uk/pdbsum/5kh7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kh7 ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/HDAC6_HUMAN HDAC6_HUMAN]] Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes (By similarity). Plays a central role in microtubule-dependent cell motility via deacetylation of tubulin.<ref>PMID:12024216</ref> <ref>PMID:17846173</ref>   In addition to its protein deacetylase activity, plays a key role in the degradation of misfolded proteins: when misfolded proteins are too abundant to be degraded by the chaperone refolding system and the ubiquitin-proteasome, mediates the transport of misfolded proteins to a cytoplasmic juxtanuclear structure called aggresome. Probably acts as an adapter that recognizes polyubiquitinated misfolded proteins and target them to the aggresome, facilitating their clearance by autophagy.<ref>PMID:12024216</ref> <ref>PMID:17846173</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Inhibitors of HDAC6 have attractive potential in numerous cancers. HDAC6 inhibitors to date target the catalytic domains, but targeting the unique zinc-finger ubiquitin-binding domain (Zf-UBD) of HDAC6 may be an attractive alternative strategy. We developed X-ray crystallography and biophysical assays to identify and characterize small molecules capable of binding to the Zf-UBD and competing with ubiquitin binding. Our results revealed two adjacent ligand-able pockets of HDAC6 Zf-UBD and the first functional ligands for this domain.

Small Molecule Antagonists of the Interaction between the Histone Deacetylase 6 Zinc-Finger Domain and Ubiquitin.,Harding RJ, Ferreira de Freitas R, Collins P, Franzoni I, Ravichandran M, Ouyang H, Juarez-Ornelas KA, Lautens M, Schapira M, von Delft F, Santhakumar V, Arrowsmith CH J Med Chem. 2017 Nov 9;60(21):9090-9096. doi: 10.1021/acs.jmedchem.7b00933. Epub , 2017 Oct 27. PMID:29019676<ref>PMID:29019676</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5kh7" style="background-color:#fffaf0;"></div>

==See Also==
*[[Histone deacetylase|Histone deacetylase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Histone deacetylase]]
[[Category: Human]]
[[Category: Arrowsmith, C M]]
[[Category: Bountra, C]]
[[Category: Edwards, A M]]
[[Category: Freitas, R Ferreira de]]
[[Category: Harding, R J]]
[[Category: Ravichandran, M]]
[[Category: Structural genomic]]
[[Category: Santhakumar, V]]
[[Category: Schapira, M]]
[[Category: Walker, J]]
[[Category: Fragment screening]]
[[Category: Hdac]]
[[Category: Hdac6]]
[[Category: Hydrolase]]
[[Category: Sgc]]