Evidence map›Paper›PMID 27454931›Full record

ArticleNature chemical biology2016

Structural insights into HDAC6 tubulin deacetylation and its selective inhibition.

Yasuyuki Miyake, Jeremy J Keusch, Longlong Wang, Makoto Saito, Daniel Hess, Xiaoning Wang, Bruce J Melancon, Paul Helquist, Heinz Gut, Patrick Matthias

Abstract read
PubMed Publisher
In one paragraph

Article in Nature chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers.

0numbers the graph read from it
0cells of the map it votes in
142citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

142 citing papers in PubMed.

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  18. Histone deacetylases and their inhibitors in kidney diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  19. Article
  20. Article

82 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Yasuyuki MiyakeFriedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
Jeremy J KeuschFriedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
Longlong WangFriedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
Makoto SaitoFriedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
Daniel HessFriedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
Xiaoning WangDepartment of Chemistry &Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA.
Bruce J MelanconDepartment of Chemistry &Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA.
Paul HelquistDepartment of Chemistry &Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA.
Heinz GutFriedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
Patrick MatthiasFriedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.

Funding

Histone Deacetylase Inhibitors for Treatment of Niemann-Pick C1 DiseaseR01NS092653 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI MAXFIELD, FREDERICK R., WALKLEY, STEVEN UPSHAW · 2015 to 2019
$2.8M
NINDS NIH HHS R01 NS092653
6 · The paper itself

Abstract

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 α-helix and a flexible tryptophan residue in the loop joining α-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 α-tubulin lysine 40 in the lumen of microtubules, but that its preferred substrate was unpolymerized tubulin.

Indexed as

AcetylationAnimalsBiocatalysisHistone Deacetylase 6Histone Deacetylase InhibitorsHistone DeacetylasesHumansHydroxamic AcidsModels, MolecularStructure-Activity RelationshipTubulinZebrafishZebrafish ProteinsHDAC6 protein, humanHDAC6 protein, zebrafishHistone Deacetylase 6Histone Deacetylase InhibitorsHistone DeacetylasesHydroxamic Acidstrichostatin ATubulinZebrafish Proteins

Identifiers

PMID27454931

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.