ArticleChemical science2021
Aromatic side-chain flips orchestrate the conformational sampling of functional loops in human histone deacetylase 8.
Article in Chemical science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 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
3 citing papers in PubMed, 6 citations in OpenAlex.
- Functional divergence and structural changes of Class IV histone deacetylases (HDACs) across the tree of life.Molecular biology and evolution · 2026Article
- Intrinsic structural dynamics dictate enzymatic activity and inhibition.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- A rationally designed synthetic antimicrobial peptide against Pseudomonas-associated corneal keratitis: Structure-function correlation.Biophysical chemistry · 2022Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Human histone deacetylase 8 (HDAC8) is a key hydrolase in gene regulation and an important drug-target. High-resolution structures of HDAC8 in complex with substrates or inhibitors are available, which have provided insights into the bound state of HDAC8 and its function. Here, using long all-atom unbiased molecular dynamics simulations and Markov state modelling, we show a strong correlation between the conformation of aromatic side chains near the active site and opening and closing of the surrounding functional loops of HDAC8. We also investigated two mutants known to allosterically downregulate the enzymatic activity of HDAC8. Based on experimental data, we hypothesise that I19S-HDAC8 is unable to release the product, whereas both product release and substrate binding are impaired in the S39E-HDAC8 mutant. The presented results deliver detailed insights into the functional dynamics of HDAC8 and provide a mechanism for the substantial downregulation caused by allosteric mutations, including a disease causing one.
Identifiers
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.