ArticleACS chemical biology2014
Compromised structure and function of HDAC8 mutants identified in Cornelia de Lange Syndrome spectrum disorders.
Article in ACS chemical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
34 citing papers in PubMed, 67 citations in OpenAlex.
- TRiC-assisted folding of class I HDAC family proteins regulated by distinct co-chaperone and cofactor networks.Science advances · 2026Article
- Investigation of All Disease-Relevant Lysine Acetylation Sites in α-Synuclein Enabled by Non-canonical Amino Acid Mutagenesis.bioRxiv : the preprint server for biology · 2025Article
- Computationally Guided Design, Synthesis, and Evaluation of Novel Non-Hydroxamic Histone Deacetylase Inhibitors, Based onPharmaceuticals (Basel, Switzerland) · 2025Article
- The Importance of Structural Water in HDAC8 for Correct Binding Pose Applied for Drug Design of Anticancer Molecules.Anti-cancer agents in medicinal chemistry · 2024Article
- A Review on Molecular Docking on HDAC Isoforms: Novel Tool for Designing Selective Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Intrinsic structural dynamics dictate enzymatic activity and inhibition.Proceedings of the National Academy of Sciences of the United States of America · 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
- A Therapeutic Perspective of HDAC8 in Different Diseases: An Overview of Selective Inhibitors.International journal of molecular sciences · 2022Review
- A Novel Intragenic Duplication in theGenes · 2022Article
- Aromatic side-chain flips orchestrate the conformational sampling of functional loops in human histone deacetylase 8.Chemical science · 2021Article
- Structural analysis of histone deacetylase 8 mutants associated with Cornelia de Lange Syndrome spectrum disorders.Journal of structural biology · 2021Article
- Article
- An in silico mechanistic insight into HDAC8 activation facilitates the discovery of new small-molecule activators.Bioorganic & medicinal chemistry · 2020Article
- Phosphorylation of Histone Deacetylase 8: Structural and Mechanistic Analysis of the Phosphomimetic S39E Mutant.Biochemistry · 2019Article
- A Genetically Encoded, Phage-Displayed Cyclic-Peptide Library.Angewandte Chemie (International ed. in English) · 2019Review
- The enzyme activity of histone deacetylase 8 is modulated by a redox-switch.Redox biology · 2019Article
- Regulation of Central Nervous System Development by Class I Histone Deacetylases.Developmental neuroscience · 2019Review
- Preparation of a new construct of human histone deacetylase 8 for the crystallization of enzyme-inhibitor complexes.Methods in enzymology · 2019Article
- HDAC8 Substrates Identified by Genetically Encoded Active Site Photocrosslinking.Journal of the American Chemical Society · 2017Article
- Asp263 missense variants perturb the active site of human phosphoglucomutase 1.The FEBS journal · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Cornelia de Lange Syndrome (CdLS) is a multiple congenital anomaly disorder resulting from mutations in genes that encode the core components of the cohesin complex, SMC1A, SMC3, and RAD21, or two of its regulatory proteins, NIPBL and HDAC8. HDAC8 is the human SMC3 lysine deacetylase required for cohesin recycling in the cell cycle. To date, 16 different missense mutations in HDAC8 have recently been identified in children diagnosed with CdLS. To understand the molecular effects of these mutations in causing CdLS and overlapping phenotypes, we have fully characterized the structure and function of five HDAC8 mutants: C153F, A188T, I243N, T311M, and H334R. X-ray crystal structures reveal that each mutation causes local structural changes that compromise catalysis and/or thermostability. For example, the C153F mutation triggers conformational changes that block acetate product release channels, resulting in only 2% residual catalytic activity. In contrast, the H334R mutation causes structural changes in a polypeptide loop distant from the active site and results in 91% residual activity, but the thermostability of this mutant is significantly compromised. Strikingly, the catalytic activity of these mutants can be partially or fully rescued in vitro by the HDAC8 activator N-(phenylcarbamothioyl)benzamide. These results suggest that HDAC8 activators might be useful leads in the search for new therapeutic strategies in managing CdLS.
Indexed as
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.