|
|
| Line 10: |
Line 10: |
| == Function == | | == Function == |
| [https://www.uniprot.org/uniprot/F8W4B7_DANRE F8W4B7_DANRE] | | [https://www.uniprot.org/uniprot/F8W4B7_DANRE F8W4B7_DANRE] |
| <div style="background-color:#fffaf0;">
| |
| == Publication Abstract from PubMed ==
| |
| 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.
| |
|
| |
| 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>
| |
|
| |
| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| |
| </div>
| |
| <div class="pdbe-citations 5g0g" 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> |