ArticleThe Journal of biological chemistry2017
HDAC8 substrate selectivity is determined by long- and short-range interactions leading to enhanced reactivity for full-length histone substrates compared with peptides.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
- The role and mechanism of histone deacetylase in COPD.Molecular and cellular biochemistry · 2026Review
- Manipulating Engram Histone Acetylation Alters Memory Consolidation.Hippocampus · 2025Article
- dCas9-HDAC8-EGFP fusion enables epigenetic editing of breast cancer cells by H3K9 deacetylation.European journal of cell biology · 2024Article
- Review
- Co-translational Installation of Posttranslational Modifications by Non-canonical Amino Acid Mutagenesis.Chembiochem : a European journal of chemical biology · 2023Article
- Lysine Deacetylase Substrate Selectivity: Distinct Interaction Surfaces Drive Positive and Negative Selection for Residues Following Acetyllysine.Biochemistry · 2023Article
- Macrocyclic Octapeptide Binding and Inferences on Protein Substrate Binding to Histone Deacetylase 6.ACS chemical biology · 2023Article
- HAT- and HDAC-Targeted Protein Acetylation in the Occurrence and Treatment of Epilepsy.Biomedicines · 2022Review
- Phage-assisted, active site-directed ligand evolution of a potent and selective histone deacetylase 8 inhibitor.Protein science : a publication of the Protein Society · 2022Article
- A Therapeutic Perspective of HDAC8 in Different Diseases: An Overview of Selective Inhibitors.International journal of molecular sciences · 2022Review
- Evidence that HDAC7 acts as an epigenetic "reader" of AR acetylation through NCoR-HDAC3 dissociation.Cell chemical biology · 2022Article
- Modulation of cellular processes by histone and non-histone protein acetylation.Nature reviews. Molecular cell biology · 2022Review
- Structure-based prediction of HDAC6 substrates validated by enzymatic assay reveals determinants of promiscuity and detects new potential substrates.Scientific reports · 2022Article
- Class I histone deacetylases (HDAC1-3) are histone lysine delactylases.Science advances · 2022Article
- Lysine Deacetylase Substrate Selectivity: A Dynamic Ionic Interaction Specific to KDAC8.Biochemistry · 2021Article
- Hydroxamic acid-modified peptide microarrays for profiling isozyme-selective interactions and inhibition of histone deacetylases.Nature communications · 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
- The Chemical Biology of Reversible Lysine Post-translational Modifications.Cell chemical biology · 2020Review
- The Roles of Histone Deacetylases and Their Inhibitors in Cancer Therapy.Frontiers in cell and developmental biology · 2020Review
- Phosphorylation of Histone Deacetylase 8: Structural and Mechanistic Analysis of the Phosphomimetic S39E Mutant.Biochemistry · 2019Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
Histone deacetylases (HDACs) catalyze deacetylation of acetyl-lysine residues within proteins. To date, HDAC substrate specificity and selectivity have been largely estimated using peptide substrates. However, it is unclear whether peptide substrates accurately reflect the substrate selectivity of HDAC8 toward full-length proteins. Here, we compare HDAC8 substrate selectivity in the context of peptides, full-length proteins, and protein-nucleic acid complexes. We demonstrate that HDAC8 catalyzes deacetylation of tetrameric histone (H3/H4) substrates with catalytic efficiencies that are 40-300-fold higher than those for corresponding peptide substrates. Thus, we conclude that additional contacts with protein substrates enhance catalytic efficiency. However, the catalytic efficiency decreases for larger multiprotein complexes. These differences in HDAC8 substrate selectivity for peptides and full-length proteins suggest that HDAC8 substrate preference is based on a combination of short- and long-range interactions. In summary, this work presents detailed kinetics for HDAC8-catalyzed deacetylation of singly-acetylated, full-length protein substrates, revealing that HDAC8 substrate selectivity is determined by multiple factors. These insights provide a foundation for understanding recognition of full-length proteins by HDACs.
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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.