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==X-ray structure of the Danio rerio histone deacetylase 6 (HDAC6; catalytic domain 2) in complex with Tubastatin A== | ==X-ray structure of the Danio rerio histone deacetylase 6 (HDAC6; catalytic domain 2) in complex with Tubastatin A== | ||
<StructureSection load='6thv' size='340' side='right'caption='[[6thv]]' scene=''> | <StructureSection load='6thv' size='340' side='right'caption='[[6thv]], [[Resolution|resolution]] 1.10Å' 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=6THV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6THV FirstGlance]. <br> | <table><tr><td colspan='2'>[[6thv]] is a 1 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=6THV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6THV FirstGlance]. <br> | ||
</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=6thv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6thv OCA], [https://pdbe.org/6thv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6thv RCSB], [https://www.ebi.ac.uk/pdbsum/6thv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6thv ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.1Å</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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=N9W:4-[(2-methyl-3,4-dihydro-1~{H}-pyrido[4,3-b]indol-5-yl)methyl]-~{N}-oxidanyl-benzamide'>N9W</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</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=6thv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6thv OCA], [https://pdbe.org/6thv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6thv RCSB], [https://www.ebi.ac.uk/pdbsum/6thv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6thv 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 == | |||
Tubastatin A, a tetrahydro-gamma-carboline-capped selective HDAC6 inhibitor (HDAC6i), was rationally designed 10 years ago, and has become the best investigated HDAC6i to date. It shows efficacy in various neurological disease animal models, as HDAC6 plays a crucial regulatory role in axonal transport deficits, protein aggregation, as well as oxidative stress. In this work, we provide new insights into this HDAC6i by investigating the molecular basis of its interactions with HDAC6 through X-ray crystallography, determining its functional capability to elevate the levels of acetylated alpha-tubulin in vitro and in vivo, correlating PK/PD profiles to determine effective doses in plasma and brain, and finally assessing its therapeutic potential toward psychiatric diseases through use of the SmartCube screening platform. | |||
Structural and in Vivo Characterization of Tubastatin A, a Widely Used Histone Deacetylase 6 Inhibitor.,Shen S, Svoboda M, Zhang G, Cavasin MA, Motlova L, McKinsey TA, Eubanks JH, Barinka C, Kozikowski AP ACS Med Chem Lett. 2020 Jan 15;11(5):706-712. doi:, 10.1021/acsmedchemlett.9b00560. eCollection 2020 May 14. PMID:32435374<ref>PMID:32435374</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6thv" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Histone deacetylase 3D structures|Histone deacetylase 3D structures]] | *[[Histone deacetylase 3D structures|Histone deacetylase 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Danio rerio]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Barinka C]] | [[Category: Barinka C]] | ||
[[Category: Motlova L]] | [[Category: Motlova L]] | ||
[[Category: Svoboda M]] | [[Category: Svoboda M]] | ||