View source for 3zns


==HDAC7 bound with TFMO inhibitor tmp942==
<StructureSection load='3zns' size='340' side='right'caption='[[3zns]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3zns]] is a 3 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=3ZNS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZNS 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]] 2.45&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=NU7:N-{[1-METHYL-4-(4-PHENYL-1,3-THIAZOL-2-YL)PIPERIDIN-4-YL]METHYL}-3-[5-(TRIFLUOROMETHYL)-1,2,4-OXADIAZOL-3-YL]BENZAMIDE'>NU7</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=3zns FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zns OCA], [https://pdbe.org/3zns PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zns RCSB], [https://www.ebi.ac.uk/pdbsum/3zns PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zns ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HDAC7_HUMAN HDAC7_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. Involved in muscle maturation by repressing transcription of myocyte enhancer factors such as MEF2A, MEF2B and MEF2C. During muscle differentiation, it shuttles into the cytoplasm, allowing the expression of myocyte enhancer factors (By similarity). May be involved in Epstein-Barr virus (EBV) latency, possibly by repressing the viral BZLF1 gene.<ref>PMID:12239305</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
In contrast to studies on class I histone deacetylase (HDAC) inhibitors, the elucidation of the molecular mechanisms and therapeutic potential of class IIa HDACs (HDAC4, HDAC5, HDAC7 and HDAC9) is impaired by the lack of potent and selective chemical probes. Here we report the discovery of inhibitors that fill this void with an unprecedented metal-binding group, trifluoromethyloxadiazole (TFMO), which circumvents the selectivity and pharmacologic liabilities of hydroxamates. We confirm direct metal binding of the TFMO through crystallographic approaches and use chemoproteomics to demonstrate the superior selectivity of the TFMO series relative to a hydroxamate-substituted analog. We further apply these tool compounds to reveal gene regulation dependent on the catalytic active site of class IIa HDACs. The discovery of these inhibitors challenges the design process for targeting metalloenzymes through a chelating metal-binding group and suggests therapeutic potential for class IIa HDAC enzyme blockers distinct in mechanism and application compared to current HDAC inhibitors.

Selective class IIa histone deacetylase inhibition via a nonchelating zinc-binding group.,Lobera M, Madauss KP, Pohlhaus DT, Wright QG, Trocha M, Schmidt DR, Baloglu E, Trump RP, Head MS, Hofmann GA, Murray-Thompson M, Schwartz B, Chakravorty S, Wu Z, Mander PK, Kruidenier L, Reid RA, Burkhart W, Turunen BJ, Rong JX, Wagner C, Moyer MB, Wells C, Hong X, Moore JT, Williams JD, Soler D, Ghosh S, Nolan MA Nat Chem Biol. 2013 Mar 24. doi: 10.1038/nchembio.1223. PMID:23524983<ref>PMID:23524983</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3zns" 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: Lobera M]]
[[Category: Madauss KP]]
[[Category: Nolan MA]]
[[Category: Pohlhaus DT]]
[[Category: Trump RP]]