ArticleNature chemical biology2016
Histone deacetylase 6 structure and molecular basis of catalysis and inhibition.
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 219 papers.
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Who cites it
219 citing papers in PubMed, 476 citations in OpenAlex.
- Design, synthesis and antiproliferative activity of oxadiazole derivatives as potent glycogen synthase kinase-3/histone deacetylase 6 dual inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- Exploration of novel hydroxamic acid-based candidates integrating chalcone scaffold cap as multitarget HDAC inhibitors: design, anti-prostatic cancer assessment,Journal of enzyme inhibition and medicinal chemistry · 2026Article
- An integrated machine learning and chemical space network approach for the design of potent epigenetic HDAC6 inhibitors for targeting neurological disorders.Molecular diversity · 2026Article
- KDAC6 alters cell morphology and motility through positive and negative modulation of F-actin distribution.FEBS open bio · 2026Article
- Hydrogen sulfide engages catalytic zinc in HDAC6 to modulate an alternative deacetylation pathway.Nature communications · 2026Article
- Ferroptosis-Pyroptosis Crosstalk in Spinal Cord Injury: Molecular Mechanisms, Emerging Connectors, and Staged Therapeutic Perspectives.Journal of molecular neuroscience : MN · 2026Review
- Mechanism-based inhibition of zinc-dependent histone deacetylases.RSC chemical biology · 2026Review
- Design, Synthesis, and Antitumor Activities of Novel Coumarin-Based Histone Deacetylase Inhibitors.Biomolecules · 2026Article
- Functional divergence and structural changes of Class IV histone deacetylases (HDACs) across the tree of life.Molecular biology and evolution · 2026Article
- Review
- Macrophage-Centric Phenotypic Screening Identifies Tetrazolone-Based HDAC6 Inhibitors That Reprogram the Tumor Immune Microenvironment and Improve Immune Checkpoint Blockade.Journal of medicinal chemistry · 2026Article
- Identification of a mechanism-based binding mode for a histone deacetylase 6 inhibitor.Nature communications · 2026Article
- Selective targeting of cortactin tandem repeat acetylation by human lysine deacetylases.The FEBS journal · 2026Article
- Design, Synthesis, and Biological Evaluation of Novel Triazine-Based Dual Histone Deacetylase/phosphatidylinositol 3-kinase Inhibitors for Breast Cancer Therapy.ChemMedChem · 2026Article
- Recommended Tool Compounds: Isoform- and Class-Specific Histone Deacetylase Inhibitors.ACS pharmacology & translational science · 2026Review
- In vitro characterization of the catalytic domain of human histone deacetylase 5.Scientific reports · 2026Article
- Capsaicin-Inspired Hydroxamate Hybrids as Selective HDAC6 Inhibitors with Antiproliferative Activity in Hematological Malignancies.ACS omega · 2026Article
- Integrated virtual screening, ADMET profiling, and molecular dynamics simulations of novel natural HDAC6 inhibitors with the potential to ameliorate skeletal muscle degeneration.Scientific reports · 2026Article
- Synthesis and crystal structure of HDAC6 selective inhibitor ofActa crystallographica. Section E, Crystallographic communications · 2026Article
- A small molecule PTER-selective inhibitor reduces food intake and body weight.bioRxiv : the preprint server for biology · 2026Article
159 more citing papers are in PubMed but not listed here.
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2 authors at 2 institutions in 2 countries.
Funding
Abstract
Histone deacetylase 6 (HDAC6) is a critical target for drug design because of its role in oncogenic transformation and cancer metastasis, and is unique among all histone deacetylases in that it contains tandem catalytic domains designated CD1 and CD2. We now report the crystal structures of CD2 from Homo sapiens HDAC6 and of CD1 and CD2 from Danio rerio HDAC6. We correlated these structures with activity measurements using 13 different substrates. The catalytic activity of CD2 from both species exhibited broad substrate specificity, whereas that of CD1 was highly specific for substrates bearing C-terminal acetyllysine residues. Crystal structures of substrate complexes yielded unprecedented snapshots of the catalytic mechanism. Additionally, crystal structures of complexes with eight different inhibitors, including belinostat and panobinostat (currently used in cancer chemotherapy), the macrocyclic tetrapeptide HC toxin, and the HDAC6-specific inhibitor N-hydroxy-4-(2-((2-hydroxyethyl)(phenyl)amino)-2-oxoethyl)benzamide, revealed surprising new insight regarding changes in Zn(2+) coordination and isozyme-specific inhibition.
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Registered trials
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.