6vnr
From Proteopedia
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==Crystal Structure of Danio rerio Histone Deacetylase 6 Catalytic Domain 2 (CD2) Complexed with Bishydroxamic Acid Inhibitor== | ==Crystal Structure of Danio rerio Histone Deacetylase 6 Catalytic Domain 2 (CD2) Complexed with Bishydroxamic Acid Inhibitor== | ||
| - | <StructureSection load='6vnr' size='340' side='right'caption='[[6vnr]]' scene=''> | + | <StructureSection load='6vnr' size='340' side='right'caption='[[6vnr]], [[Resolution|resolution]] 1.94Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VNR OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[6vnr]] 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=6VNR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VNR FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9430132Å</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=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=R5G:N-hydroxy-1-{[4-(hydroxycarbamoyl)phenyl]methyl}-1H-indole-6-carboxamide'>R5G</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=6vnr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vnr OCA], [https://pdbe.org/6vnr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vnr RCSB], [https://www.ebi.ac.uk/pdbsum/6vnr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vnr ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/F8W4B7_DANRE F8W4B7_DANRE] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | We report the synthesis and evaluation of a class of selective multi-target agents for the inhibition of HDAC6, HDAC8 and HDAC10. The concept for this study grew out of a structural analysis of the two selective inhibitors Tubastatin A (HDAC6/10) and PCI-34051 (HDAC8), which we recognized share the same N -benzylindole core. Hybridization of the two inhibitor structures resulted in dihydroxamic acids with benzyl-indole and -indazole core motifs. These substances exhibit potent activity on HDAC6, HDAC8 and HDAC10, while retaining selectivity over HDAC1, HDAC2 and HDAC3. The best substance inhibited viability of the SK-N-BE(2)C neuroblastoma cell line with an IC 50 value similar to a combination treatment with Tubastatin A and PCI-34051. This compound class establishes proof of concept for such hybrid molecules and may serve as a starting point for the further development of enhanced HDAC6/8/10 inhibitors. | ||
| + | |||
| + | Design and Synthesis of Dihydroxamic Acids as HDAC6/8/10 Inhibitors.,Miller AK, Morgen M, Steimbach RR, Geraldy M, Hellweg L, Sehr P, Ridinger J, Witt O, Oehme I, Herbst-Gervasoni CJ, Osko JD, Porter NJ, Christianson DW, Gunkel N ChemMedChem. 2020 Apr 29. doi: 10.1002/cmdc.202000149. PMID:32348628<ref>PMID:32348628</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6vnr" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Histone deacetylase 3D structures|Histone deacetylase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Danio rerio]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Christianson DW]] | [[Category: Christianson DW]] | ||
[[Category: Osko JD]] | [[Category: Osko JD]] | ||
[[Category: Porter NJ]] | [[Category: Porter NJ]] | ||
Current revision
Crystal Structure of Danio rerio Histone Deacetylase 6 Catalytic Domain 2 (CD2) Complexed with Bishydroxamic Acid Inhibitor
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