ArticleJournal of the American Chemical Society2014
Inhibition and mechanism of HDAC8 revisited.
Article in Journal of the American Chemical Society, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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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.
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.
Who cites it
27 citing papers in PubMed, 57 citations in OpenAlex.
- Hydrogen sulfide engages catalytic zinc in HDAC6 to modulate an alternative deacetylation pathway.Nature communications · 2026Article
- Zinc Affinity of Benzamide-Based Histone Deacetylase Inhibitors: A DFT Study.Molecules (Basel, Switzerland) · 2026Article
- Unraveling the Catalytic Mechanism and Substrate Selectivity of HDAC10: A Dual-Filter Approach for Polyamine Deacetylation.JACS Au · 2025Article
- Lysine Deacetylase Substrate Selectivity: Distinct Interaction Surfaces Drive Positive and Negative Selection for Residues Following Acetyllysine.Biochemistry · 2023Article
- Endogenous expression of inactive lysine deacetylases reveals deacetylation-dependent cellular mechanisms.PloS one · 2023Article
- Lysine Deacetylase Substrate Selectivity: A Dynamic Ionic Interaction Specific to KDAC8.Biochemistry · 2021Article
- Aromatic side-chain flips orchestrate the conformational sampling of functional loops in human histone deacetylase 8.Chemical science · 2021Article
- Critical review of non-histone human substrates of metal-dependent lysine deacetylases.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Review
- Bifunctional HDAC Therapeutics: One Drug to Rule Them All?Molecules (Basel, Switzerland) · 2020Review
- Multitarget Anticancer Agents Based on Histone Deacetylase and Protein Kinase CK2 inhibitors.Molecules (Basel, Switzerland) · 2020Article
- Formation of Unstable and very Reactive Chemical Species Catalyzed by Metalloenzymes: A Mechanistic Overview.Molecules (Basel, Switzerland) · 2019Review
- Optimal Substrate-Trapping Mutants to Discover Substrates of HDAC1.Chembiochem : a European journal of chemical biology · 2019Article
- Overexpressed HDAC8 in cervical cancer cells shows functional redundancy of tubulin deacetylation with HDAC6.Cell communication and signaling : CCS · 2018Article
- Computer-Aided Drug Design in Epigenetics.Frontiers in chemistry · 2018Review
- Purification of metal-dependent lysine deacetylases with consistently high activity.Protein expression and purification · 2018Article
- Chelatable trace zinc causes low, irreproducible KDAC8 activity.Analytical biochemistry · 2018Article
- Lysine Deacetylases Exhibit Distinct Changes in Activity Profiles Due to Fluorophore Conjugation of Substrates.Biochemistry · 2017Article
- Development of a Potent and Selective HDAC8 Inhibitor.ACS medicinal chemistry letters · 2016Article
- Substrate specificity and function of acetylpolyamine amidohydrolases from Pseudomonas aeruginosa.BMC biochemistry · 2016Article
- General Base-General Acid Catalysis in Human Histone Deacetylase 8.Biochemistry · 2016Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Histone deacetylases (HDACs) have found intense interest as drug targets for a variety of diseases, but there is disagreement about basic aspects of the inhibition and mechanism of HDACs. QM/MM calculations of HDAC8 including a large QM region provide a model that is consistent with the available crystal structures and structure-activity relationships of different HDAC inhibitors. The calculations support a spontaneous proton transfer from a hydroxamic acid to an active site histidine upon binding to the zinc. The role of the H142/D176 catalytic dyad as the general base of the reaction is elucidated. The reasons for the disagreements between previous proposals are discussed. The results provide detailed insights into the unique mechanism of HDACs, including the role of the two catalytic dyads and function of the potassium near the active site. They also have important implications for the design of novel inhibitors for a number of HDACs such as the class IIa HDACs.
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What OpenQuestion holds
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.