ArticleBiochemistry2014
Structure of the p300 histone acetyltransferase bound to acetyl-coenzyme A and its analogues.
Article in Biochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 62 citations in OpenAlex.
- Article
- Processes and therapeutic perspectives of acylation modifications of lysine and cysteine in tumors.Cell communication and signaling : CCS · 2026Review
- Epigenetic regulators in cancer therapy and progression.NPJ precision oncology · 2025Review
- Tailoring a CRISPR/Cas-based Epigenome Editor for Programmable Chromatin Acylation and Decreased Cytotoxicity.bioRxiv : the preprint server for biology · 2024Article
- Dux activates metabolism-lactylation-MET network during early iPSC reprogramming with Brg1 as the histone lactylation reader.Nucleic acids research · 2024Article
- Robinetin Alleviates Metabolic Failure in Liver through Suppression of p300-CD38 Axis.Biomolecules & therapeutics · 2024Article
- First-in-Class Selective Inhibitors of the Lysine Acetyltransferase KAT8.Journal of medicinal chemistry · 2023Article
- Article
- KATs off: Biomedical insights from lysine acetyltransferase inhibitors.Current opinion in chemical biology · 2023Review
- Molecular and functional characterization of an evolutionarily conserved CREB-binding protein in the Lymnaea CNS.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Pleiotropic effects of mitochondria in aging.Nature aging · 2022Review
- 3,4-dihydroxytoluene, a metabolite of rutin, suppresses the progression of nonalcoholic fatty liver disease in mice by inhibiting p300 histone acetyltransferase activity.Acta pharmacologica Sinica · 2021Article
- Remodelin Is a Cryptic Assay Interference Chemotype That Does Not Inhibit NAT10-Dependent Cytidine Acetylation.ACS medicinal chemistry letters · 2021Article
- The Biological Significance of Targeting Acetylation-Mediated Gene Regulation for Designing New Mechanistic Tools and Potential Therapeutics.Biomolecules · 2021Review
- Identification of lysine isobutyrylation as a new histone modification mark.Nucleic acids research · 2021Article
- Carnosol Is a Novel Inhibitor of p300 Acetyltransferase in Breast Cancer.Frontiers in oncology · 2021Article
- Discovery, Structure-Activity Relationship, and Biological Activity of Histone-Competitive Inhibitors of Histone Acetyltransferases P300/CBP.Journal of medicinal chemistry · 2020Article
- Regulation of Thermogenic Adipocyte Differentiation and Adaptive Thermogenesis Through Histone Acetylation.Frontiers in endocrinology · 2020Review
- Immunometabolism in the pathogenesis of systemic lupus erythematosus.Journal of translational autoimmunity · 2020Review
- TET2 missense variants in human neoplasia. A proposal of structural and functional classification.Molecular genetics & genomic medicine · 2019Article
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
The p300 and CBP transcriptional coactivator paralogs (p300/CBP) regulate a variety of different cellular pathways, in part, by acetylating histones and more than 70 non-histone protein substrates. Mutation, chromosomal translocation, or other aberrant activities of p300/CBP are linked to many different diseases, including cancer. Because of its pleiotropic biological roles and connection to disease, it is important to understand the mechanism of acetyl transfer by p300/CBP, in part so that inhibitors can be more rationally developed. Toward this goal, a structure of p300 bound to a Lys-CoA bisubstrate HAT inhibitor has been previously elucidated, and the enzyme's catalytic mechanism has been investigated. Nonetheless, many questions underlying p300/CBP structure and mechanism remain. Here, we report a structural characterization of different reaction states in the p300 activity cycle. We present the structures of p300 in complex with an acetyl-CoA substrate, a CoA product, and an acetonyl-CoA inhibitor. A comparison of these structures with the previously reported p300/Lys-CoA complex demonstrates that the conformation of the enzyme active site depends on the interaction of the enzyme with the cofactor, and is not apparently influenced by protein substrate lysine binding. The p300/CoA crystals also contain two poly(ethylene glycol) moieties bound proximal to the cofactor binding site, implicating the path of protein substrate association. The structure of the p300/acetonyl-CoA complex explains the inhibitory and tight binding properties of the acetonyl-CoA toward p300. Together, these studies provide new insights into the molecular basis of acetylation by p300 and have implications for the rational development of new small molecule p300 inhibitors.
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