ArticleJournal of the American Chemical Society2013
Loop interactions and dynamics tune the enzymatic activity of the human histone deacetylase 8.
Article in Journal of the American Chemical Society, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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.
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Who cites it
18 citing papers in PubMed, 39 citations in OpenAlex.
- A dual catalytic architecture promotes C-2 stereoinversion of CDP-glucose by the CDP-tyvelose 2-epimerase from Thermodesulfatator atlanticus.The Journal of biological chemistry · 2026Article
- Binding mechanism and distant regulation of histone deacetylase 8 by PCI-34051.Communications biology · 2025Article
- Crucial Structural Understanding for Selective HDAC8 Inhibition: Common Pharmacophores, Molecular Docking, Molecular Dynamics, and Zinc Binder Analysis of Selective HDAC8 Inhibitors.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2025Review
- Intrinsic structural dynamics dictate enzymatic activity and inhibition.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Lysine Deacetylase Substrate Selectivity: Distinct Interaction Surfaces Drive Positive and Negative Selection for Residues Following Acetyllysine.Biochemistry · 2023Article
- Continuous enzyme activity assay for high-throughput classification of histone deacetylase 8 inhibitors.Exploration of targeted anti-tumor therapy · 2023Article
- Methionine 274 Is Not the Determining Factor for Selective Inhibition of Histone Deacetylase 8 (HDAC8) by L-Shaped Inhibitors.International journal of molecular sciences · 2022Article
- Structural mass spectrometry decodes domain interaction and dynamics of the full-length Human Histone Deacetylase 2.Biochimica et biophysica acta. Proteins and proteomics · 2022Article
- 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
- A distal regulatory region of a class I human histone deacetylase.Nature communications · 2020Article
- Phosphorylation of Histone Deacetylase 8: Structural and Mechanistic Analysis of the Phosphomimetic S39E Mutant.Biochemistry · 2019Article
- Real-time monitoring of conformational transitions of single-molecule histone deacetylase 8 with nanocircuits.Chemical communications (Cambridge, England) · 2017Article
- Biochemical and structural characterization of HDAC8 mutants associated with Cornelia de Lange syndrome spectrum disorders.Biochemistry · 2015Article
- Variable active site loop conformations accommodate the binding of macrocyclic largazole analogues to HDAC8.Biochemistry · 2015Article
- Compromised structure and function of HDAC8 mutants identified in Cornelia de Lange Syndrome spectrum disorders.ACS chemical biology · 2014Article
- Inhibition and mechanism of HDAC8 revisited.Journal of the American Chemical Society · 2014Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
The human histone deacetylase 8 (HDAC8) is a key hydrolase in gene regulation and has been identified as a drug target for the treatment of several cancers. Previously the HDAC8 enzyme has been extensively studied using biochemical techniques, X-ray crystallography, and computational methods. Those investigations have yielded detailed information about the active site and have demonstrated that the substrate entrance surface is highly dynamic. Yet it has remained unclear how the dynamics of the entrance surface tune and influence the catalytic activity of HDAC8. Using long time scale all atom molecular dynamics simulations we have found a mechanism whereby the interactions and dynamics of two loops tune the configuration of functionally important residues of HDAC8 and could therefore influence the activity of the enzyme. We subsequently investigated this hypothesis using a well-established fluorescence activity assay and a noninvasive real-time progression assay, where deacetylation of a p53 based peptide was observed by nuclear magnetic resonance spectroscopy. Our work delivers detailed insight into the dynamic loop network of HDAC8 and provides an explanation for a number of experimental observations.
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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.