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5g0h

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==Crystal structure of Danio rerio HDAC6 CD2 in complex with (S)- trichostatin A==
==Crystal structure of Danio rerio HDAC6 CD2 in complex with (S)- trichostatin A==
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<StructureSection load='5g0h' size='340' side='right' caption='[[5g0h]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
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<StructureSection load='5g0h' size='340' side='right'caption='[[5g0h]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[5g0h]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5G0H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5G0H FirstGlance]. <br>
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<table><tr><td colspan='2'>[[5g0h]] 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=5G0H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5G0H FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=E1Z:S-TRICHOSTATIN+A'>E1Z</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5g0f|5g0f]], [[5g0g|5g0g]], [[5g0i|5g0i]], [[5g0j|5g0j]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=E1Z:S-TRICHOSTATIN+A'>E1Z</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<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=5g0h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5g0h OCA], [http://pdbe.org/5g0h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5g0h RCSB], [http://www.ebi.ac.uk/pdbsum/5g0h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5g0h ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5g0h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5g0h OCA], [https://pdbe.org/5g0h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5g0h RCSB], [https://www.ebi.ac.uk/pdbsum/5g0h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5g0h ProSAT]</span></td></tr>
</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/F8W4B7_DANRE F8W4B7_DANRE]
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We report crystal structures of zebrafish histone deacetylase 6 (HDAC6) catalytic domains in tandem or as single domains in complex with the (R) and (S) enantiomers of trichostatin A (TSA) or with the HDAC6-specific inhibitor nexturastat A. The tandem domains formed, together with the inter-domain linker, an ellipsoid-shaped complex with pseudo-twofold symmetry. We identified important active site differences between both catalytic domains and revealed the binding mode of HDAC6 selective inhibitors. HDAC inhibition assays with (R)- and (S)-TSA showed that (R)-TSA was a broad-range inhibitor, whereas (S)-TSA had moderate selectivity for HDAC6. We identified a uniquely positioned alpha-helix and a flexible tryptophan residue in the loop joining alpha-helices H20 to H21 as critical for deacetylation of the physiologic substrate tubulin. Using single-molecule measurements and biochemical assays we demonstrated that HDAC6 catalytic domain 2 deacetylated alpha-tubulin lysine 40 in the lumen of microtubules, but that its preferred substrate was unpolymerized tubulin.
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Structural insights into HDAC6 tubulin deacetylation and its selective inhibition.,Miyake Y, Keusch JJ, Wang L, Saito M, Hess D, Wang X, Melancon BJ, Helquist P, Gut H, Matthias P Nat Chem Biol. 2016 Jul 25. doi: 10.1038/nchembio.2140. PMID:27454931<ref>PMID:27454931</ref>
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==See Also==
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*[[Histone deacetylase 3D structures|Histone deacetylase 3D structures]]
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 5g0h" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Gut, H]]
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[[Category: Danio rerio]]
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[[Category: Helquist, P]]
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[[Category: Large Structures]]
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[[Category: Hess, D]]
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[[Category: Gut H]]
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[[Category: Keusch, J J]]
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[[Category: Helquist P]]
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[[Category: Matthias, P]]
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[[Category: Hess D]]
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[[Category: Melancon, B J]]
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[[Category: Keusch JJ]]
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[[Category: Miyake, Y]]
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[[Category: Matthias P]]
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[[Category: Saito, M]]
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[[Category: Melancon BJ]]
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[[Category: Wang, L]]
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[[Category: Miyake Y]]
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[[Category: Wang, X]]
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[[Category: Saito M]]
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[[Category: Cell cycle]]
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[[Category: Wang L]]
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[[Category: Histone]]
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[[Category: Wang X]]
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[[Category: Histone deacetylase]]
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Current revision

Crystal structure of Danio rerio HDAC6 CD2 in complex with (S)- trichostatin A

PDB ID 5g0h

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