ArticleEuropean journal of medicinal chemistry2015
Enzyme kinetics and inhibition of histone acetyltransferase KAT8.
Article in European journal of medicinal chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 35 citations in OpenAlex.
- KAT8-mediated epigenetic modifications: Physiological functions, heterogeneity in disease, and advances in targeted development.iScience · 2026Review
- Inhibition of Histone Lysine Acetyltransferases by Coenzyme A Analogs.Molecules (Basel, Switzerland) · 2026Article
- Reversible Acetylation of Non-histone Proteins in Human Cancers.Results and problems in cell differentiation · 2025Review
- First-in-Class Selective Inhibitors of the Lysine Acetyltransferase KAT8.Journal of medicinal chemistry · 2023Article
- Metabolic and Cellular Compartments of Acetyl-CoA in the Healthy and Diseased Brain.International journal of molecular sciences · 2022Review
- Catalysis by protein acetyltransferase Gcn5.Biochimica et biophysica acta. Gene regulatory mechanisms · 2021Review
- Substrate Scope for Human Histone Lysine Acetyltransferase KAT8.International journal of molecular sciences · 2021Article
- Gcn5-RelatedFrontiers in molecular biosciences · 2021Article
- The evolving metabolic landscape of chromatin biology and epigenetics.Nature reviews. Genetics · 2020Review
- Effect of lysine side chain length on histone lysine acetyltransferase catalysis.Scientific reports · 2020Article
- Lysine Acetyltransferase Inhibitors From Natural Sources.Frontiers in pharmacology · 2020Review
- The Regulatory Effects of Acetyl-CoA Distribution in the Healthy and Diseased Brain.Frontiers in cellular neuroscience · 2018Review
- The relevance of KEuropean journal of medicinal chemistry · 2017Article
- A 6-alkylsalicylate histone acetyltransferase inhibitor inhibits histone acetylation and pro-inflammatory gene expression in murine precision-cut lung slices.Pulmonary pharmacology & therapeutics · 2017Article
- The multifaceted role of lysine acetylation in cancer: prognostic biomarker and therapeutic target.Oncotarget · 2016Review
- The histone acetyltransferase p300 inhibitor C646 reduces pro-inflammatory gene expression and inhibits histone deacetylases.Biochemical pharmacology · 2016Article
- Histone acetyltransferases: challenges in targeting bi-substrate enzymes.Clinical epigenetics · 2016Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Lysine acetyltransferase 8 (KAT8) is a histone acetyltransferase (HAT) responsible for acetylating lysine 16 on histone H4 (H4K16) and plays a role in cell cycle progression as well as acetylation of the tumor suppressor protein p53. Further studies on its biological function and drug discovery initiatives will benefit from the development of small molecule inhibitors for this enzyme. As a first step towards this aim we investigated the enzyme kinetics of this bi-substrate enzyme. The kinetic experiments indicate a ping-pong mechanism in which the enzyme binds Ac-CoA first, followed by binding of the histone substrate. This mechanism is supported by affinity measurements of both substrates using isothermal titration calorimetry (ITC). Using this information, the KAT8 inhibition of a focused compound collection around the non-selective HAT inhibitor anacardic acid has been investigated. Kinetic studies with anacardic acid were performed, based on which a model for the catalytic activity of KAT8 and the inhibitory action of anacardic acid (AA) was proposed. This enabled the calculation of the inhibition constant Ki of anacardic acid derivatives using an adaptation of the Cheng-Prusoff equation. The results described in this study give insight into the catalytic mechanism of KAT8 and present the first well-characterized small-molecule inhibitors for this HAT.
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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.